Background

Myocardial infarction (MI), defined as myocardial cell death due to significant and sustained ischemia, affects people without regard to geographic area and is one of the leading causes of death and disability both in developed and developing countries [1, 2]. MI could lead to reduced quality of life, severe long-term functional impairment, and adverse health outcomes including recurrent MI, ventricular arrhythmias, heart failure, and sudden cardiac death [3, 4]. Therefore, individuals who experienced MI are usually at heightened risk for psychological distress, of which anxiety is a major manifestation [5, 6].

Anxiety, characterized by excessive worry, fear, tension or panic, is common among MI patients [6]. Accumulating evidence have convergently suggested that in addition to the negative effects on quality of life, elevated anxiety symptoms in MI were associated with a wide range of subsequent poor prognosis, including increased in-hospital arrhythmic and ischemic complications, poor attendance at cardiac rehabilitation, lower adherence to many important risk-reducing recommendations after MI, higher rates of future coronary events and cardiac rehospitalization, as well as increased risk for cardiac and all-cause mortality [7,8,9,10,11]. A prior meta-analysis in 2010 of 12 prospective studies covering 5,750 MI patients indicated that increased anxiety symptoms following MI could put individuals at 71%, 23% and 47% higher risk for new cardiac events, cardiac mortality and all-cause mortality, respectively [12]. Therefore, early identification of anxiety symptoms, as well as timely and effective psychological interventions for those with increased anxiety symptoms is crucial among MI patients, which could be facilitated by offering an accurate and reliable estimate on the prevalence of moderate to high anxiety symptoms among MI patients given its contribution to allocating psychological resources properly.

There has been an increasing number of publications examining the prevalence of moderate to high anxiety symptoms among MI patients over the last two decades. However, their reported prevalence varied markedly from 18 to 57% [13,14,15,16,17,18]. Several possible reasons may contribute to the disparate findings seen, including socio-demographic characteristics such as sex, living status and education level, cardiovascular risk factors such as smoking status, hypertension, diabetes and hypercholesterolemia, characteristics of the index MI, the instrument used to assess anxiety, timing of anxiety assessment, and a history of previous psychiatric disorder [9, 13, 19,20,21,22,23]. Another reason may be the varying methodological quality across these studies. In this regard, a pooled estimate combing all relevant findings of the individual studies is warranted. Accordingly, this study sought to synthesize the evidence on the prevalence of moderate to high anxiety symptoms among MI patients using meta-analytic methods.

Methods

This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Search Strategy

Comprehensive electronic searches of the PubMed, Embase and Web of Science databases were performed from their inception to February 2021. The search strategy included a combination of subject headings and free-text regarding anxiety and MI, and the specific search terms were customized across databases (Additional file 1). The reference lists of two relevant reviews [12, 24] and full-text articles were extracted and further screened to obtain more potentially eligible studies.

Eligibility Criteria

The inclusion criteria for this meta-analysis were: (1) the study design was cross-sectional, case-control, baseline data from longitudinal studies, or baseline data from randomized control trials before allocating the groups; (2) the primary target population was MI patients and the diagnosis of MI was affirmed by medical records; (3) the study identified moderate to high anxiety symptoms by validated self-report questionnaires with appropriate psychometric quality and established threshold information; (4) the study provided sufficient information to calculate the prevalence of moderate to high anxiety symptoms among MI patients and the corresponding sample size; (5) the sample size of subjects with MI was at least 200; and (6) the study was published in English in a peer-reviewed journal. Case reports, comments, letters to the editor, or conference abstracts were excluded. Additionally, if data overlapped among multiple publications, the earliest publication was included in this meta-analysis. Two raters independently screened and assessed the eligibility of the individual studies using the preceding established criteria and any disagreement between them was resolved by discussing with the third rater.

Data Extraction

The outcome of this meta-analysis was the prevalence of moderate to high anxiety symptoms among MI patients identified by either above the established cut-off values or above the norm-referenced values of the self-report questionnaires, and for the purpose of this study, data extracted from the eligible studies were: (1) study-level characteristics including the first author, publication year, study country, study design, sample source, number of subjects with anxiety, sample size of subjects with MI, the prevalence of anxiety among MI patients, and the methodological quality; (2) sample socio-demographic characteristics including age, sex, living status, and education level; (3) sample MI- and anxiety- related characteristics including a history of previous MI, the instrument used to assess anxiety, type of anxiety, and timing of anxiety assessment; and (4) sample characteristics on cardiovascular risk factors including smoking status, hypertension, diabetes and hypercholesterolemia, and a history of previous psychiatric disorder. Two raters independently extracted the preceding data and any disagreement between them was resolved by discussing with the third rater.

Quality Assessment

The methodological quality of the eligible studies was assessed using the Loney scale [25]. This scale has been widely used to appraise the methodological quality of observational studies which examine the prevalence of health-related outcomes. It consists of 8 questions comprehensively assessing the representativeness of sample, the validity of methods, and the interpretation of the results. Each question is answered by “Yes”, “No” or “Unclear”, with 1 point assigned for each answer of “Yes” and 0 point assigned for each answer of “No” or “Unclear”. Accordingly, the maximum score of this scale is 8 points, with more points indicating higher methodology quality. A total score of 0 to 3, 4 to 6, and 7 to 8 points suggests low, moderate and high quality, respectively.

Statistical Analyses

All statistical analyses were conducted using the “meta” and “metafor” packages of R software-version 3.6.0. Between-study heterogeneity was analyzed using the Cochran’s Q test and \({I}^{2}\) statistic [26]. Specifically, a P value of < 0.05 of the Cochran’s Q test indicated significant heterogeneity, and a value of ≥ 25%, ≥ 50%, and ≥ 75% of the \({I}^{2}\) statistic suggested low, moderate, and high heterogeneity, respectively [27]. If between-study heterogeneity was not significant, data on the reported prevalence of moderate to severe anxiety symptoms among the individual studies were combined by a fixed effects model using Freeman-Tukey double arcsine method. Otherwise, a random effects model was applied [28].

If between-study heterogeneity was high across the eligible studies, meta-regression analyses and subgroup analyses were conducted to examine the contribution of possible moderators to the heterogeneity. Specifically, meta-regression analyses were performed using the restricted maximum-likelihood estimator method according to some continuous moderators such as publication year, mean age of subjects, proportion of male subjects, proportion of subjects with first-time MI, and quality assessment score, whereas subgroup analyses were performed according to some categorical moderators such as sex, living status, educational level, a history of previous MI, hypertension, diabetes, and hypercholesterolemia. For moderators tested in the meta-regression analyses, the included studies should be at least 10, while for moderators tested in subgroup analyses, the included studies should be at least 2. Furthermore, the disparity in each subgroup was tested by chi-square test, and a P value of < 0.05 was considered as significant [29].

Publication bias was examined not only visually by funnel plot but also objectively by the Egger’s linear test and Begg’s rank test [30,31,32]. Sensitivity analyses were performed to explore the robustness of the pooled results both by removing each eligible study serially and removing the eligible studies with low methodological quality [29].

Results

Search Results

A total of 4,875 studies were initially retrieved through the systematic search described above, and 846 of which were duplicates. After reviewing abstracts, 85 full-text articles were shortlisted for the eligibility assessment. Among the 85 full-text articles, 23 were excluded for not reporting the prevalence of moderate to severe anxiety symptoms in MI, 21 were excluded for neither using a validated self-report questionnaire to assess moderate to high anxiety symptoms nor diagnosing by clinicians, 8 were excluded for a sample size of less than 200 and 15 were excluded for repeated data. Finally, 18 eligible articles were included in this meta-analysis (Fig. 1).

Fig. 1
figure 1

PRISMA flow chart of study selection

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Study Characteristics

The characteristics of the 18 eligible studies were shown in Table 1, and the reference list of the 18 eligible studies was shown in the Additional file 2. They were published from 1996 to 2020 and conducted in 14 countries including Canada, United Kingdom (UK), Netherlands, Australia, Japan, South Korea, United States of America (USA), Norway, Sweden, Pakistan, Iran, Denmark, German, and China. Fifteen of the 18 eligible studies were longitudinal studies, 2 were cross-sectional studies, and 1 was a case-control study. Furthermore, 17 were hospital-based, and 1 was population-based.

Table 1 Characteristics of the 18 eligible studies
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In terms of the instrument used to assess anxiety, 4 identified moderate to severe anxiety symptoms using the Spielberger’s State-Trait Anxiety Inventory (STAI), 4 using the anxiety subscale of Hospital Anxiety and Depression Scale (HADS), 2 using the anxiety subscale of Brief Symptom Inventory (BSI), 1 using the Hamilton Anxiety Rating Scale (HARS), 1 using the anxiety subscale of 90-item Symptom Check List (SCL-90), 1 using the of the phobic anxiety subscale of Middlesex Hospital Questionnaire (MHQ), 1 using Beck Anxiety Inventory (BAI), 1 using the anxiety subscale of Multiple Affect Adjective Checklist (MAACL), 1 using the Generalized Anxiety Disorder scale (GAD-7), 1 using used the Spielberg state anxiety questionnaire, and 1 using the Zung Self-Rating Anxiety Scale (SAS).

For most eligible studies, anxiety was assessed during their hospitalization. The sample mean age varied from 58 to 67 years, the sample proportion of male subjects varied from 41.9% to 100%, and the sample proportion of subjects with first-time MI varied from 60% to 100% across the 18 eligible studies.

Regarding the methodological quality assessment, the total score ranged from 3 to 7 points across the 18 eligible studies, with 1 scoring 7 points, 10 scoring 5 points, 5 scoring 4 points and 2 scoring 3 points, respectively. Only one eligible study was population-based and the study subjects was regarded as a whole population with an unbiased sampling frame. For all eligible studies, anxiety was assessed by standard instruments, and 11 recruited a sample size of more than 300 (Table 2).

Table 2 Methodological quality assessment of the 18 eligible studies
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Pooled Prevalence of Moderate to Severe Anxiety Symptoms among MI Patients

The 18 eligible studies covered a total of 8,532 MI patients and 3,443 of them were identified with moderate to severe anxiety symptoms. Between-study heterogeneity was significant and high (\({I}^{2}\)=98.8%, P < 0.05) across the 18 eligible studies with the reported prevalence ranging from 9.6% to 69.17%. The lowest prevalence was reported in a hospital-based study in Netherlands in 2014 [33], and the highest prevalence was reported in a hospital-based study in Canada in 1996 which used the STAI to assess anxiety [6]. The pooled prevalence of moderate to severe anxiety symptoms among MI patients was 38.08% (95% confidence interval [CI]: 28.82–47.81%) by a random-effects model (Fig. 2).

Fig. 2
figure 2

Forest plot presenting the pooled prevalence of moderate to severe anxiety symptoms among MI patients

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Meta-Regression Analyses

The results of meta-regression analyses were shown in Table 3. Mean age of subjects (β = −0.030, P = 0.101), proportion of male subjects (β = 0.214, P = 0.584), proportion of subjects with first-time MI (β = 0.170, P = 0.755), quality assessment score (β = −0.036, P = 0.500), study design (β = -0.046, P = 0.525), and sample source (β = −0.168, P = 0.409) were not moderators contributing significantly to the heterogeneity, while publication year (β = −0.014, P = 0.041) was significant moderators which contributed 16.11% to the heterogeneity, respectively.

Table 3 Meta-regression analyses of the contribution of possible moderators to the overall heterogeneity
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Subgroup Analyses

The results of subgroup analyses were shown in Table 4. The pooled prevalence of moderate to severe anxiety symptoms among studies from Europe/UK, North America/Australia, and Asia was 25.23% (95CI%: 15.70–36.14%), 47.40% (95%CI: 33.50-61.52%), and 51.81% (95CI%: 31.75–71.57%), respectively. The pooled prevalence among studies that used STAI, the anxiety subscale of HADS, and the anxiety subscale of BSI to assess anxiety was 53.90% (95CI%: 35.87–71.43%), 26.25% (95CI%: 19.36–33.78%), and 47.17% (95CI%: 4.46–49.74%), respectively. The pooled prevalence among female and male subjects was 47.02% (95CI%: 26.68–67.89%) and 40.71% (95CI%: 24.49–58.03%), respectively. Furthermore, the pooled prevalence among subjects with and without a history of previous MI was 62.33% (95CI%: 37.57–84.15%) and 54.96% (95CI%: 32.31–76.58%), respectively. Between-study heterogeneity was high among studies included in most of the subgroups. Nonetheless, studies using the anxiety subscale of BSI to assess anxiety were homogenous (\({I}^{2}\)=0.0, P = 0.317).

Table 4 Subgroup analyses on the prevalence of anxiety among patients with myocardial infarction
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The pooled prevalence of moderate to severe anxiety symptoms varied significantly in terms of geographic region, instrument used to assess anxiety, methodological quality, sex, education level, a history of previous MI and hypercholesterolemia (P < 0.05). In particular, the pooled prevalence was significantly higher among studies from North America/Australia and Asia (vs. studies from Europe/UK), among studies with low methodological quality (vs. studies with moderate to high methodological quality, among studies using STAI to assess anxiety (vs. studies using the anxiety subscale of HADS, and studies using the anxiety subscale of BSI, respectively), among female subjects (vs. male subjects), among subjects with education level of below secondary school (vs. subjects with education level of secondary school or above), among subjects with a history of previous MI (vs. subjects without a history of previous MI), and among subjects with hypercholesterolemia (vs. subjects without hypercholesterolemia).

Publication Bias and Sensitivity Analysis

Publication bias was not observed in this meta-analysis based on the findings of Egger’s linear test (t = −0.630, P = 0.538) and Begg’s rank test (z = −0.190, P = 0.850) and the funnel plot was symmetrical (Fig. 3).

Fig. 3
figure 3

Funnel plot of the 18 eligible studies in these meta- analyses

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By removing the 18 eligible studies one-by-one, the pooled results varied from 36.26% (95CI%: 27.51–45.49%) to 40.10% (95CI%: 30.99–49.56%), and the \({I}^{2}\) statistic values varied from 98.6% to 98.9%. In particular, by removing the only one population-based study, the pooled result was 39.00% (95CI%: 29.28–49.17%) and the \({I}^{2}\) statistic value was 98.8%, and by removing the only one study which included exclusively male subjects, the pooled result was 36.93% (95CI%: 27.45–46.95%) and the \({I}^{2}\) statistic value was 98.8%. Furthermore, by excluding 2 eligible studies with low methodological quality, the pooled prevalence decreased from 38.08% (95% CI: 28.82–47.81%) to 36.62% (95%CI: 26.71–47.14%), and the \({I}^{2}\) statistic value was 98.9%.

Discussion

Main Findings

This meta-analysis synthesized the evidence on the prevalence of moderate to severe anxiety symptoms among MI patients. Eighteen eligible studies conducted in 14 countries with a total of 8,532 MI patients were included, of which 3,443 were identified with moderate to severe anxiety symptoms. The reported prevalence ranged markedly from 9.6% to 69.17% across the 18 eligible studies, and the pooled prevalence of moderate to severe anxiety symptoms among MI patients was 38.08% (95%CI: 28.82–47.81%) by a random-effects model. To the best of our knowledge, this is the first meta-analysis to explore the pooled prevalence of moderate to severe anxiety symptoms among MI patients.

This study suggested that the pooled prevalence of moderate to severe anxiety symptoms among MI patients (38.08%, 95%CI: 28.82–47.81%) was lower than that among patients with heart failure (55.5%, 95% CI: 48.08–62.83%) [34], but higher than that among patients with many other somatic diseases such as osteoarthritis (21.3%, 95%CI: 15.5–28.5%) [35], prostate cancer (27.04%, 95%CI: 24.26–30.01%) [36], and multiple sclerosis (34.2%, 95%CI: 23.2–47.1%) [37]. Based on the high pooled prevalence of moderate to severe anxiety symptoms in MI and the potential role of increased anxiety symptoms in subsequent adverse outcomes among MI patients, it is highly recommended for researchers, clinicians and policy-makers to take effective measures to screen anxiety symptoms at an early stage after MI and implement psychological interventions for those with elevated anxiety symptoms accordingly.

When examining the study-level characteristics, subgroup analyses suggested that the pooled prevalence of moderate to severe anxiety symptoms in MI differed significantly by geographic region and methodological quality, which were in line with many previous meta-analyses with similar topic [37,38,39]. For example, Boeschoten et al. [37] conducted a meta-analysis exploring the pooled prevalence of depression among patients with multiple sclerosis and found that it was lower among studies from Europe. The varying socioeconomic level and sociocultural background may contribute largely to the regional disparity in anxiety prevalence. Additionally, it has been well established that methodological quality of the individual studies plays an important role in the stability of the pooled results [40]. In particular, studies with low methodological quality often employ biased sampling strategies with limited sample sizes, thus inducing various types of selection bias and ultimately overestimate the pooled effect size [41]. Therefore, it is recommended for future studies to employ unbiased sampling strategies with large sample sizes (e.g., recruiting subjects from the whole population with a sample size of > 300).

Consistent with previous meta-analyses exploring the pooled prevalence of anxiety [38, 42], this study showed that the pooled prevalence of moderate to severe anxiety symptoms in MI differed significantly by sample socio-demographic characteristics including sex and education level, which could be explained by the sex differences in psychosocial, personalistic and behavioral factors, such as coping strategies, social support, personality traits, and resilience, as well as the sex differences in hormone levels and the varying utilization of neural resources in response to stress between males and females [43,44,45]. Therefore, when allocating psychological resources targeting anxiety following MI, sex and education level should be taken into consideration. In particular, female subjects or those with education level of below secondary school should be given special attention.

Additionally, this study showed that the pooled prevalence of moderate to severe anxiety symptoms varied significantly in terms of the instrument used to assess anxiety. Similar findings were observed in previous meta-analyses exploring the pooled prevalence of anxiety among patients with systemic lupus erythematosus and adults with traumatic brain injury [46, 47]. The varying psychometric quality and cut-off values, as well as the different conceptual and operational definitions of anxiety across the self-repot instruments used to assess anxiety could account for the disparate findings seen, suggesting the need for standardizing the measurement of moderate to severe anxiety symptoms among MI patients.

With regard to MI-related factors and cardiovascular risk factors, this study found that those with a history of previous MI and hypercholesterolemia exhibited higher pooled prevalence of moderate to severe anxiety symptoms than their counterparts. Similar findings were observed in a prior meta-analysis exploring the pooled prevalence of depression among MI patients [39]. MI is a serious disease with poor health-related outcomes such as heart failure and sudden cardiac death, and those with recurrent MI or comorbid with other diseases may exhibit higher risk for adverse cardiac events [48, 49], as a consequence of which, adverse psychological outcomes including depression and anxiety are more likely to occur. These findings significantly stressed the need for researchers, clinicians and policy-makers to pay special attention to those with a history of previous MI and hypercholesterolemia when allocating psychological resources targeting anxiety following MI.

In terms of the source of heterogeneity, meta-regression analyses showed that publication year was a significant moderator contributing 16.11% to the heterogeneity, and subgroup analyses showed that studies using the anxiety subscale of BSI to assess anxiety were homogenous. These findings suggested that when evaluating and comparing the prevalence of moderate to severe anxiety symptoms in MI across multiple publications, the differences in publication year, instrument used to assess anxiety should be considered.

Strengths and Limitations

Some limitations should be noted. Firstly, the overall heterogeneity was high across the 18 eligible studies. However, the absence of publication bias and low sensitivity of the pooled results, as well as the identified role of publication year and instrument used to assess anxiety, could add great reliability when interpreting the findings of this meta-analysis. Secondly, though some individual studies showed that the timing of anxiety assessment and a history of previous psychiatric disorder were associated with the prevalence of anxiety in MI [20, 21, 23], relevant data were unable to be synthesized either due to the varying indicators or due to the limited number of studies reporting such data. Therefore, future studies should find more factors which may contribute to the anxiety prevalence among MI patients and measuring such data using consistently standardized indicators. Thirdly, it should be stressed here that regarding the sample source, all but one eligible study was hospital-based. Therefore, whether the findings of this study could be generalized into population-based studies should be further explored on the condition of the presence of an adequate number of population-based studies. Nonetheless, in a prior meta-analysis exploring the pooled prevalence of anxiety following spinal cord injury, it was found that sample source did not affect the pooled results significantly [50]. Furthermore, since the disparities in all subgroups was tested univariately without controlling potential confounders, relevant findings should be interpreted with caution.

Conclusions

Anxiety is common among MI patients with nearly two fifth suffering from moderate to severe anxiety symptoms. The reported prevalence of moderate to severe anxiety symptoms is highly heterogenous across the eligible studies, which could be partially explained by publication year and the instrument used to assess anxiety. Additionally, the pooled prevalence of moderate to severe anxiety symptoms varied significantly by geographic region, instrument used to assess anxiety, methodological quality, sex, education level, a history of previous MI and hypercholesterolemia, stressing the need for researchers, clinicians and policy-makers to take the preceding factors into account when comparing the prevalence of moderate to severe anxiety symptoms in MI across multiple publications and allocating psychological resources targeting anxiety among MI patients. Future efforts should work towards exploring more factors affecting anxiety and standardizing the measurement of moderate to severe anxiety symptoms among MI patients. Furthermore, more population-based studies with high methodological quality are warranted.