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 Table of Contents  
Year : 2022  |  Volume : 6  |  Issue : 2  |  Page : 52-57

Anxiety in individuals with cardiovascular diseases: A narrative review and expert opinion

Department of Psychiatry and Behavioral Sciences; Department of Medicine, Duke University Health Systems, Durham, North Carolina, USA

Date of Submission01-Apr-2022
Date of Acceptance11-Apr-2022
Date of Web Publication16-May-2022

Correspondence Address:
Dr. Wei Jiang
Department of Psychiatry and Behavioral Sciences, Duke University Health Systems, Durham 27710; Department of Medicine, Duke University Health Systems, Durham 27710
North Carolina, USA
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/hm.hm_5_22

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Anxiety is a commonly prevalent mental problem in patients with cardiovascular diseases (CVD), but its significance and clinical management have been neglected until recently. Similar to depression, anxiety has been demonstrated to be prevalent and hinging the quality of life and optimal outcome of patients with CVD. Although research evidence is still limited, clinical management for depression may be adopted for the care of anxiety in patients with CVD. Special attention needs to be paid when diagnosing anxiety disorder in patients with CVD because the fear may be a normal reaction of these patients and anxiety may manifest somatically.

Keywords: Anxiety, cardiovascular diseases, mindfulness cognitive behavior therapy, selective serotonin reuptake inhibitors

How to cite this article:
Jiang W. Anxiety in individuals with cardiovascular diseases: A narrative review and expert opinion. Heart Mind 2022;6:52-7

How to cite this URL:
Jiang W. Anxiety in individuals with cardiovascular diseases: A narrative review and expert opinion. Heart Mind [serial online] 2022 [cited 2023 Mar 27];6:52-7. Available from: http://www.heartmindjournal.org/text.asp?2022/6/2/52/345285

  Introduction Top

Aside from depression, anxiety is another commonly experienced emotional activity of human lives and plays significant role in the biopsychosocial interactive system of human health. Much attention has been paid to depression in cardiovascular health in medical literature over many years, and our understanding of anxiety with cardiovascular health has been on the rise recently. Anxiety bears a similar prevalence of depression, according to the WHO 2017 Global Health Estimates. As the total number of people with depression was estimated to exceed 300 million in 2015 globally, nearly the same number suffers from a range of anxiety disorders. Since many people experience both conditions simultaneously (comorbidity), it is inappropriate to simply add these two figures together to arrive at a total for common mental disorders. More importantly, the number of persons with common mental disorders globally is going up, particularly in lower-income countries, because the population is growing and more people are living to the age when depression and anxiety most commonly occur. People experiencing subclinical anxiety or fear, worry, and feeling of uncertain are countless and exhausting health-care resources, which was not accounted in the WHO 2017. This review aims at summarizing the recent understanding of anxiety with cardiovascular diseases (CVD). Opinion of clinical management will be shared as well.

  Prevalence of Anxiety in Individuals with Cardiovascular Diseases Top

Data accumulated particularly since the beginning of the 21st century consistently demonstrate that anxiety is prevalent in patients with CVD.[1] For instance, in a meta-analysis, Tully et al. showed that the point prevalence of any anxiety disorders in CVD patients was 16%. The prevalence of generalized anxiety disorder (GAD) and panic disorder was much higher in CVD patients than in the general population (7.97 vs. 3.1%, and 6.81 vs. 2.7%, respectively).[2] In a sample of 804 patients with stable coronary heart disease (CHD), Frasure–Smith[3] identified that 5.3% had GAD and 41.4% had elevated anxiety symptoms. Following an episode of acute coronary syndrome (ACS), 20%–30% of patients were found to experience elevated levels of anxiety.[4],[5] While post-ACS anxiety may be transient for some patients, in half of the cases, anxiety persists for up to 1-year postevent.[4] Koivula et al. identified 25% of CHD patients experiencing elevated anxiety symptoms before the coronary artery bypass grafting procedure.[6] In a recent meta-analysis of 38 studies, Easton et al. estimated that 32% of patients with heart failure (HF) experience elevated levels of anxiety, and 13% meet the criteria for an anxiety disorder.[7] Anxiety also affects approximately 20% of patients with more advanced HF who require implantation of a left ventricular assist device to support their cardiac function.[8],[9] In patients who have undergone implantation of an implantable cardioverter defibrillator to prevent the development of lethal arrhythmias, approximately 20%–40% of them have elevated anxiety symptoms.[10] Post-stroke patients are another vulnerable population that has high anxiety, as data show that anxiety following a stroke or transient ischemic attack occurs in about 24% of patients[11] and is a distressing problem associated with poorer health-related quality of life.[12]

  Clinical Significance of Anxiety in Patients with Cardiovascular Diseases Top

The clinical significance of anxiety in CVD patients is not as clearly delineated as the impact of depression and recently emerged evidence indicates that anxiety may be a risk factor for CVD. For instance, Frasure–Smith and Lesperance[3] followed patients with stable coronary artery disease for 2 years, and found that not only depression but also anxiety predicted a greater risk of major adverse cardiac events such as cardiac death, myocardial infarction, or cardiac arrest in those patients. In a meta-analysis that comprised 20 studies and 249,846 individuals with a mean follow-up period of 11.2 years, Roest et al. found that anxious persons were at risk of CHD (hazard ratio [HR] random: 1.26; 95% confidence interval [CI]: 1.15–1.38; P = 0.0001) and cardiac death (HR: 1.48; 95% CI: 1.14–1.92; P = 0.003), independent of demographic variables, biological risk factors, and health behaviors.[13] The association between anxiety and nonfatal myocardial infarction was not statistically significant (HR: 1.43; 95% CI: 0.85–2.40; P = 0.180). Several years later, Emdin et al. conducted a meta-analysis on 46 cohort studies and found anxiety was associated with a 41% higher risk of cardiovascular mortality and CHD, a 71% higher risk of stroke, and a 35% higher risk of HF.[14] Several studies have pointed out that anxiety is not only associated with CVD-related mortality but also associated with all-cause mortality.[15],[16],[17],[18] Furthermore, the findings of many studies[13],[14],[19],[20] have indicated that anxiety disorders may also be an independent risk factor in the development of CVD. Nevertheless, the association of anxiety and increased overall mortality has not been consistently demonstrated. For example, after adjusting for publication bias based on 36 cohort studies, Miloyan et al. found no increase in overall mortality in anxiety disorders.[21] Jiang et al.[22] measured symptoms of anxiety with the Spielberger State-Trait Anxiety Inventory scale and symptoms of depression with the Beck Depression Inventory (BDI) scale in 291 patients who had chronic HF and were hospitalized because of cardiac events. The team then followed these patients up for all-cause mortality over 1 year. The State-A and Trait-A scores were moderately correlated with the BDI score (State-A, r = 0.52; Trait-A, r = 0.59; P < 0.01) but had no relation with 1-year mortality by Cox-proportional analysis. BDI scores, however, significantly predicted increased mortality during 1-year follow-up (HR, 1.04 for each 1-unit increase; P < 0.01). In a community sample of 11,643 German adults between 40 and 80 years of age, Reiner et al.[23] investigated the association of chronic anxiousness with CVD and mortality. They assessed anxiety using the two-item version of the GAD-7.[24],[25] The two items were 1. “Feeling nervous, anxious or on edge” and 2. “Not being able to stop or control worrying” with scores rated from 0 = “not at all,” 1 = “several days,” 2 = “over half the days,” and 3 = “nearly every day” of each. The assessment was conducted at baseline and then repeated during the next 2.5 years. The authors reported that 12% of the participants reported consistently raised (chronic) anxiousness over 2.5 years. The chronic anxiousness was linked to the new onset of CVD in men but did not predict all-cause mortality[23] over a 5-year follow-up.

In addition to the CV impact, anxiety can bring on many somatic complaints that complexes the clinical management of these patients. This has been an important public health issue because anxiety impairs the daily function of these patients and worsens their quality of life that is greater than those without anxiety.[26] Furthermore, the repeated utilization of health-care services by patients with non-CVD rooted symptoms leads to a substantial financial burden, with the annual cost of such patients' evaluations measured in the billions.[27],[28]

  Clinical Management of Anxiety in Patients with Cardiovascular Diseases Top

Diagnostic consideration: What should we know about anxiety before diagnosis?

At the most basic level, anxiety is an emotion, a secondary emotion of the primary emotion of fear. The most important distinction between fear and anxiety may be the timeframe. Fear is the response to a danger that is currently detected in the immediate, present moment. In contrast, anxiety refers to the anticipation of some potential threat that may, or may not, happen in future. Anxiety reflects the anticipation of fear and represents an adaptive attempt to prevent the fear-provoking circumstance from occurring. In an anxious state, people are readying themselves and preparing themselves to cope with a future problem or dilemma that they anticipate will cause some kind of harm if not prevented from occurring. In this respect, anxiety is a normal, beneficial emotion. Having fear and anxiety under certain specific conditions is not all abnormal. Therefore, a health-care provider needs to grab the conceptual differences and convey them to his/her patients effectively.

While emotion is a subjective state of being, emotion is often associated with changes in feelings, behaviors, thoughts, and physiology, and experienced in varying degrees of intensity. Anxiety is an emotion characterized by feelings of tension, worried thoughts, and physical changes such as increased blood pressure, heart rate, and muscle intensity dysregulation. When anxiety recurs and/or persists, namely anxiety disorders, individuals with such conditions usually have recurring intrusive thoughts or concerns. They may avoid certain situations out of worry. They may also have physical symptoms such as sweating, trembling, dizziness, or a rapid heartbeat. If not effectively managed, anxiety can become a debilitating disorder, often associated with excessive worry, fear, isolation, depression, substance abuse, suicidal ideation, and other forms of psychopathology.[29]

Individuals with anxiety may present with various physiological manifestations such as excessive thirst, stomach upset, loose bowel movement, frequent urination, headaches, hot flushes or chills, pounding heart, chest pain, increased heart rate, fatigue, poor sleep, muscle tension and/or pain, excessive sweating, hyperventilation or shortness of breath, dizziness, dilated pupils, heightened senses, hypertension, trembling, and tingling. Mental symptoms can include the following:[29],[30] easily losing patience; difficulty in concentrating; thinking constantly about worst outcomes, sleep disturbance, depression, preoccupied or obsessed with one subject, compelled to perform rituals and routines repeatedly, excessive worry about many things (for example bad things happening to self or loved ones), restless, jumpy, irritability, angry, crying, clinging, avoidance, tantrums, fear of death or loss of control, intense and/or irrational fears, smothering feeling, feeling of choking, verbal or physical aggression, avoid people, places, or activities, refusal to go to school, camp, and sleepover, take a long time to calm down, etc.

Above is a brief overview of the basic knowledge of anxiety in patients with CVD.

Commonly prevalent anxiety disorders in patients with cardiovascular diseases

The study by Goodwin et al.[31] has by far provided the most reliable evidence showing the commonly prevalent anxiety disorders in patients with CVD. Through analyzing the data drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of 43,093 US civilian noninstitutionalized participants aged 18 and older who underwent systematic diagnostic interviews, the authors found that CVD was associated with these three anxiety disorders, i.e., GAD (odds ratio [OR] = 1.48 [1.09, 2.01]), panic disorder (OR = 1.46 [1.12, 1.91]), and specific phobia (OR = 1.29 [1.04, 1.59]. Adjustment disorder with anxiety (with/out depression) can be a commonly encountered anxiety disorder in CVD practice.

What should we do?

The most critical point a clinician needs to pay close attention to when working with a CVD patient is to keep anxiety and/or depression on the differential list. There have been a number of self-administered anxiety scales, but their utilization in CVD patients has not been investigated. Based on studies from other populations and experience of clinical practice, this author recommended to consider the GAD Questionnaire (GAD-7)[32] or the Beck Anxiety Inventory (BAI).[33] The GAD-7 has seven items, primarily following features listed in the Diagnostic and Statistical Manual of Mental Disorders, and BAI has 21 items that include more somatic complaints and more inclusive of various anxiety disorders.[34],[35],[36] Moreover, the Hospital Anxiety and Depression Scale (HADS) was designed for the detection and assessment of those mood disorders in the setting of hospitals and clinics and can be self-administered easily in CVD patients for both anxiety and depression assessment.[37]

  Anxiety Intervention in Patients with Cardiovascular Diseases Top

Qualified research evidence regarding whether interventions are effective in anxiety improvement appears promising.

Farquhar and Blumenthal et al. conducted a systematic review in 2018 when there were only four interventional studies included on elevated anxiety symptoms in patients with CHD.[38] Two of the four used the same database[39],[40] [Table 1]. In addition, Jiang et al., at Duke University Health systems, have conducted the UNWIND (UNderstanding the benefits of exercise and escitalopram in anxious patients WIth coroNary heart Diseasetrial) (ClinicalTrials. gov NCT02516332) between January 2016 and May 2020. The UNWIND intended to evaluate the efficacy of aerobic exercise and escitalopram, compared with matched placebo, in improving anxiety symptoms and reducing the risk for adverse clinical events in patients with CHD and anxiety. This study randomized eligible patients to aerobic exercise (N = 60), escitalopram (N = 60), or matched placebo pill (N = 30) for 12 weeks.[41] The UNWIND trial is the first study using anxiolytic medication to treat cardiac patients with elevated anxiety. The primary results of the UNWIND appeared in JAMA Psychiatry in November 2021,[42] revealing that both the exercise group and escitalopram group demonstrated greater reductions in HADS-A (exercise, −4.0; 95% CI, −4.7 to − 3.2; escitalopram, −5.7; 95% CI, −6.4 to −5.0) compared with the matched control group that was taking a placebo (−3.5; 95% CI, −4.5 to − 2.4; P = 0.03). Further, the escitalopram group demonstrated a less anxiety compared with the exercise group (−1.67; 95% CI, −2.68 to −0.66; P = 0.002). Moreover, the UNWIND trial demonstrated a significant postintervention group differences in 24-h urinary catecholamines (exercise z score = 0.05; escitalopram z score = −0.24; and placebo z score = 0.36), with greater reductions in both exercise group and escitalopram group compared with the placebo group (P = 0.01) and greater reductions in the escitalopram group compared with the exercise group (P = 0.04). The trial also showed that escitalopram in these participants was safe.
Table 1: Studies examined anxiolytic treatment in patients with cardiovascular diseases

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Knapp et al. conducted a Cochran review in 2017 to look at available evidence of anxiety intervention in poststroke patients. The authors identified three trials (four interventions) involving 196 participants with stroke and comorbid anxiety.[43] The first trial, described as a pilot study, randomized 21 community-dwelling stroke survivors to 4 weeks of using a relaxation CD (music records) versus on a waitlist control. Using HADS, the study reported a reduction in anxiety at 3 months among participants who had used the relaxation CD (mean [standard deviation (SD)] 6.9 [±4.9] vs. ones in the waitlist 11.0 [±3.9]), Cohen's d = 0.926, P = 0.001. The second trial randomized 81 participants with comorbid anxiety and depression to paroxetine, paroxetine plus psychotherapy, or standard care. Mean levels of anxiety severity scores by the Hamilton Anxiety Scale (HAM-A) at follow-up were 5.4 (SD ± 1.7), 3.8 (SD ± 1.8), and 12.8 (SD ± 1.9), respectively (P < 0.01). The third trial randomized 94 stroke patients, with comorbid anxiety depression, to receive buspirone hydrochloride or standard care. At follow-up, the mean levels of anxiety by the HAM-A were 6.5 (SD ± 3.1) and 12.6 (SD ± 3.4) in the two groups, respectively, which represents a significant difference (P < 0.01). Half of the participants receiving paroxetine experienced adverse events that included nausea, vomiting, or dizziness and 14% of those receiving buspirone experienced nausea or palpitations. Knapp et al.[43] concluded that the quality of the evidence was very low, as each study included a small number of participants, particularly the study of relaxation therapy. Pharmacological studies presented limited data to allow judgment of selection, performance, and detection bias.

Many investigators have speculated that mentally driven intervention may improve the prognostic outcomes of CVD over the years, but there have been no definitive data to approve it. The obstacles of conducting outcome clinical trials are hard to overcome at present. Some investigators took steps to look at the effects on intermediate biomarkers. For example, The REMIT (Responses of Mental Stress-Induced Myocardial Ischemia to Escitalopram, Clinicaltrials. gov NCT00574847) study demonstrated a 6-week escitalopram, compared to matched placebo, reduced mental stress-induced myocardial ischemia that is a predictor of increased major CV events.[44] Elzib et al. summarized the findings of seven clinical studies, indicating selective serotonin reuptake inhibitors (SSRIs) and other antidepressant medications improve the neuromotor skills of patients post stroke.[45] Kamarck et al.[46] randomized 159 healthy adults with elevated hostility scores to citalopram or placebo for a 2-month period, and found that citalopram favorably changed metabolic risk factors, including waist circumference, glucose, high-density lipoprotein cholesterol, triglycerides, and insulin resistance. In each variable, the active drug group showed significant favorable changes over time and the placebo group did not [Table 2]. All of these metabolic changes were significantly mediated by treatment-related changes in body mass index (in most cases, P < 0.01).[46]
Table 2: Changes in metabolic risk factors as a function of a 2-month experimental intervention (citalopram versus placebo)

Click here to view

The controversy on the safety of mentally driven interventions in patients with CVD remains. Nevertheless, randomized clinical trials testing SSRIs, mindfulness practice, and cognitive-behavioral interventions have shown that they are safe compared with matched placebos. However, other studies, especially longitudinal observational studies, tend to question significant side effects, particularly related to concerning metabolic alterations.[47] These inconsistent and concerning data require more investigations and caution of clinical practice. The phenomenon of citalopram prolonging the QT interval has not been validated among other SSRIs.[48]

From a clinical practice perspective, the biggest change over a couple of decades may be that SSRI has emerged to be the first-line anxiolytic agent. Benzodiazepines may be used in acute situations to improve active panic attacks briefly. A combination of SSRIs and mindfulness cognitive behavior therapy (MCBT) is considered most effective for anxiety with/out of depression, but MCBT's effective implementation in CVD services has been very challenging.

  Summary Top

Anxiety, similar to depression, is prevalent in as well as a risk for patients with CVD. Although definitively evidence-based practice regarding effective management is not yet in place, limited data gained from randomized clinical trials support SSRIs and MCBT are effective and relatively safe. Nonmental health practice clinicians need to be vigilant when working with CVD patients and ascertain the provision of applicable interventions targeting on anxiety reduction once indicated. Utilization of SSRIs needs to start with the lowest doses with titration on tolerability and side effect profile. Particular cautions of using SSRIs include, nor exclusively: (1) their antiplatelet function when patients take other anticoagulated medications, and (2) risk of serotonin syndrome when patients use other serotonin agents.

Ethical statement

Ethical statement is not applicable for this article.

Financial support and sponsorship


Conflicts of interest

Prof. Wei Jiang is the Editorial Board member of the Heart and Mind journal. The article was subject to the journal's standard procedures, with peer review handled independently of Prof. Wei Jiang and their research groups. There are no conflicts of interest.

  References Top

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[PUBMED]  [Full text]  
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