Depression, anxiety, and quality of life after percuataneous coronary interventions.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the world. However, some fascinating advances in the field of cardiology have not only added years to people's life but life to years as well. Percutaneous coronary intervention (PCI), commonly known as coronary angioplasty is a nonsurgical procedure used to treat stenotic coronary arteries. In recent years, PCI has become the preferred modality of treatment for occluded coronary arteries. However, there has been growing interest in the quality of life (QOL) issues for those who undergo such procedures. Depression, anxiety, vital exhaustion, hostility, anger, and acute mental stress have been evaluated as risk factors for the development and progression of CAD. Further, they also have strong bearing toward recovery from an acute coronary event. The current article discusses the role of depression, anxiety, and QOL of patients undergoing PCI. Copyright:

Cardiovascular diseases (CVDs) are the leading cause of death worldwide and of which coronary artery disease (CAD) leads from the front.[1] Global Burden of Disease study estimates age-standardized CVD death rate of 272 per 100 000 population in India which is higher than the global average of 235/100,000 population. CAD in Indian subcontinent is of particular concern because of its accelerated build up, earlier age of onset and high mortality.[2] Despite wide heterogeneity in the prevalence of cardiovascular risk factors across different regions, CAD has emerged as the leading cause of death in all the parts of India. In addition, it has been estimated that most of these deaths are preventable.[3] Studies are underway in many parts of the world to reduce the number of cardiac deaths. Besides taking preventive measures, prompt diagnosis and intervention are particularly important. The relationship of psychological symptoms with CAD and its corrective procedures is well known. The combined effect of both cardiac and psychological illness is more than the sum total of both the illnesses put together and generally indicates poor outcome.[4] Therefore, besides other rehabilitative measures, screening and treatment for depression is mandated by American Heart Association (AHA) as well as Cardiological Society of India.

SURGICAL AND NONSURGICAL CARDIAC INTERVENTIONS

In 1953, William Mustard performed first carotid to coronary direct surgical approach to the coronary circulation. It was followed by the surgical myocardial revascularization procedure to repair an obstruction of the left main coronary artery. There have been many refinements of the technique in the last few decades and off late robotic CABG is slowly gaining ground.[56] While surgical techniques were in the forefront, Andreas Grüntzig, a German cardiologist, performed the first coronary angioplasty in 1977.[6] In India, PCIs are growing at the rate of 14% annually and in 2014, a total of 248,152 coronary interventions were performed.[2] The increase in primary PCIs also corresponds with an increase in hospital mortality rates. The mortality rate in 2014 was 1.25% as compared to 0.89% in 2013.[2] There have been rapid advances in PCI techniques with introduction of drug-eluting stents (DESs) which lower the chances of restenosis after stenting. Local release of rapamycin and its derivatives or of paclitaxel from a polymer matrix on the stent reduces inflammation and smooth muscle cell proliferation within the stent.[7]

CONCEPT OF DEPRESSION AND ANXIETY IN MEDICAL SETTINGS

According to the International Classification for Diseases eleventh edition,[8] depression is characterized by low mood and/or anhedonia (loss of interest in activities that once were pleasurable) that lasts for 2 weeks or more and leads to significant functional impairment. In addition, the patient may complain of negative thoughts, disturbed sleep, easy fatigability, body aches, gastrointestinal disturbances, or sexual problems. Anxiety on the other hand refers to feeling of apprehension and unease. Anxiety presents with somatic, physiological, and cognitive symptoms. Somatic symptoms include tremulousness, palpitations, and hyperhydrosis. The physiological component refers to tachycardia, hyperventilation, increased muscular tension, and an irritable bladder. The cognitive symptom is that of worry which refers to undue fear of something untoward happening. It is not uncommon to find both depression and anxiety on a continuum. Cardiovascular symptoms and anxiety have always been closely related. In fact, this relationship has had an interesting history under the different names of “irritable heart,” “da costa syndrome” and “neurocirculatory asthenia.”[910]

When a person is medically ill, it may be considered natural for the patient to feel depressed, worried, and debilitated. However, normal reaction to an illness needs to be differentiated from a pathological entity although it may not always be easy. Many roadblocks hinder the diagnosis and treatment of depression in the medically ill.[11] For example, patients may think it is normal to feel sad after developing a life-threatening illness such as CAD. Therefore, they may not mention it during routine follow-up. Similarly, clinicians may focus on the medical illness rather than the psychological symptoms (i.e., treat only the medical illness since it caused the depression and that depression will be all right once medical condition improves). The issue has been debated extensively. Depression in medically ill has been consistently found to be an independent entity having adverse overall effect on the course and outcome. Both 6 months and lifetime prevalence of depression in patients with any medical illness is almost double than that of individuals without medical illness.[12] Further, patients having both depression and medical illness are still depressed at 6 and 12 months as compared to controls having only depression and no medical illness.[13]

DEPRESSION AND CARDIAC INTERFACE

Modern medical literature is replete with scientific articles highlighting the role of psychological factors in chronic medical conditions including CAD. Sudden cardiac death due to acute emotional stress is well known.[14] Numerous studies have strongly supported the hypothesis that depression increases the risk of the development and progression of CAD.[15] Psychiatric patients too have increased incidence of CAD.[16] In brief, evidence favoring the positive correlation of CAD and depression is too robust to be refuted. The reported prevalence of depression in patients with cardiac disease is quite variable. A meta-analysis of over 20 studies of patients with preexisting CAD demonstrates a 2–6 fold risk for adverse coronary outcomes, including MI and death, when complicated by depression.[17] A dose response relationship appears to exist between the severity of depressive symptoms after AMI or unstable angina and the risk of death over 5-year follow-up.[18] Young adults, women, and those with past or family history of depression may be particularly vulnerable to develop depression among patients of CAD.[19] Other factors which have been cited include social isolation, past history of coronary event, obesity and diabetes.[2021]

PATHOPHYSIOLOGY OF CAD IN DEPRESSION

The exact link between heart and psychological factors is not really known. More than 300 years ago, William Harvey was the first one to describe this association and his observations still hold true. In 1628 he wrote “Every affection of the mind that is attended with pain or pleasure, hope or fear is the cause of an agitation, whose influence extends to the heart.”[22] Probable mechanisms are as under:

Behavioral mechanisms

Which include social isolation, physical inactivity, poor adherence, and smoking.

Biological mechanisms which include: (a) Hypothalamic–pituitary–adrenal axis dysregulation manifesting by raised levels of circulating cortisol and loss of the usual diurnal variation in cortisol level; (b) Toxic effects of elevated cortisol on the coronary artery endothelium leading to the development of plaque; (c) Disordered platelet aggregation leading to increased thrombus formation; and (d) Genetic studies linking CAD and serotonin transporter.

In brief, dysregulation of HPA axis and disordered platelet aggregation and other factors lead to heightened risk of atherosclerosis (biological predictors). When combined with behavioral predictors of poor dietary habits, poor adherence, reduced activity, smoking and excessive drinking, process of thrombus formation is hastened which leads to CAD.[2324]

HEALTH RELATED QUALITY OF LIFE IN CAD

Quality of life (QOL) is a subjective measure of happiness and has significant impact on many decisions of daily life. The factors that play a role in QOL include financial security, job satisfaction, family life, health, and safety. Although many resources may not be always available, humans adapt according to the reality and adjust their expectations. This enables people to maintain a reasonable QOL even during adversity. The issue gains importance in the realms of medical care as many chronic medical conditions usually lead to poor QOL and require significant adaptation and change in lifestyle. Health-related QOL (HRQOL) is a multi-dimensional concept that includes domains related to physical, mental, emotional, and social functioning.[25] Besides direct measures of health, life expectancy and causes of death, the HRQOL focuses on the impact of health status on QOL. HRQOL serves as a common benchmark, against which the impact of medical conditions on the overall health and QOL is measured. Clinicians often work together to improve the HRQOL of the patients besides treating the disease per se. The various parameters which are usually measured by HRQOL instruments are items on self-rated health, physical HRQOL, mental HRQOL, fatigue, pain, emotional distress, social activities, and roles.[2627] They can broadly be divided into following domains along with the negative consequences if there are deficits in the mentioned domains [Table 1].

Table 1

Domains of health related quality of life: Their attributes and effects of deficits in the domain

Domain	Attribute	Deficits in domain
Physical	Able to move around freely	Limited mobility
Functional	Functions as useful member of the team	Unable to perform at optimum level
Psychological	Free of worries, thinks positively	Anxiety and Depression
Social	Meeting social responsibilities and expectations	Decreased social interaction, dependency, feeling of being a burden
Spiritual	Meaning and purpose of life	Excessive religiosity, wishing for magical cure
Recreational	Enjoy recreational activities	Poor participation in recreational activities

CAD imposes a substantial burden on HRQOL, although most of it can be modulated by effective prevention, intervention and rehabilitation. Following a chronic illness, women generally have worse HRQOL than men.[19] Social isolation and a lack of social support are poor prognostic factors in CAD.[20] On the other hand, social support may be protective against development and progression of CAD. A meta-analysis showed that social support has significant and substantial influence on all-cause mortality (hazard ratio 1.59; 95% confidence interval [CI] 1.21–2.08) even after controlling for somatic risk factors.[28] Diabetes mellitus is a common comorbid medical condition in patients of CAD and when the condition occurs together the effects may get compounded. Such patients are vulnerable for depression, anxiety, and psychosocial problems.[21] Obesity plays an important role in the metabolic syndrome (abdominal obesity, high blood pressure, dyslipidemia, and insulin resistance). As BMI increases, so does the risk of CAD. Chronic stress at work, perceived low position in the professional hierarchy and being engaged in work shifts including night shifts are well-known risk factors for CAD in men.[29.30] Type “D” personality is a strong predictor of CAD. This kind of personality is characterized by having chronic tendency toward negative feeling such as depression, anxiety, and irritability.[31] Vital exhaustion, a term intended to denote a state of tiredness and demoralization and increased irritability spanning over many years.[32] It has been found that vital exhaustion is significantly related with new cardiac events in men by a factor of 1.7. A prospective study of 4084 men and 5479 women in the Copenhagen City Heart Study revealed that vital exhaustion is a risk factor for CAD.[33] Sexual activity though not contraindicated in heart patients, generally remains a low priority thus affecting comforting in family settings. A recent study analyzed sexuality of patients in heart patients in terms of KiTOMi (acronym for kissing, touching, oral stimulation, masturbation, vaginal, or anal intercourse) and found that it is adversely affected in patients undergoing PCIs.[34]

IDENTIFICATION OF DEPRESSION IN MEDICAL SETTINGS

It is commonly said that eyes do not see what the mind does not know. In spite of plethora of literature highlighting the role of depression in precipitating and aggravating CAD, depression is commonly missed. Therefore, it is not strange that <15% of depressed patients were accurately identified by their treatment teams, and only 11% received treatment with antidepressants.[35] The common barriers[11] to mental health care can be broadly classified into four broad categories [Table 2].

Table 2

Barriers to identification of depression in medical settings

Barriers to care	Possible factors
Communication factors	Language, awareness and attitude
Clinician factors	Lack of awareness, compassion, shortage of time, apprehension about patient’s reaction towards psychiatric referral
Patient factors	Alexithymia, shame, stigma, learned helplessness, financial constraints
System factors	Facilities for cross referral and financial considerations

Effective communication patterns based on awareness, attitudinal patterns, and time constraints are integral to ensure that patients are able to express their concerns and symptoms in an effective manner. Clinician factors could be lack of awareness, shortage of time, inner apprehension about referring patient to the psychiatrist because of stigma. Patient factors could be alexithymia (inability to express feelings), shame about reporting psychiatric symptoms, learned helplessness, and inability to pay for additional expenditure of psychiatric treatment. The system factors are by and large most important. Facilities for cardiology care are generally limited to tertiary hospitals, although there are many private hospitals which offer these services as well. Tertiary care centers generally are extremely busy leaving limited time for a detailed psychiatric workup. In the private set up, the concept of package system for the coronary intervention procedures generally restricts any add on expenditure although lack of awareness may be equally responsible.[36]

SCREENING FOR DEPRESSION, ANXIETY AND QUALITY OF LIFE ISSUES

From the above discussion, it is amply clear that psychological issues are commonly present in patients with CAD and are associated with increased cardiovascular morbidity and mortality. Maximum research has been conducted on depression as a syndrome in cardiac patients keeping anxiety and psychosocial aspects on its continuum. Therefore, screening for depression can be an effective means toward the early detection in patients of CAD.[37] AHA recommends routine two stage screening of patients of CAD with a two question simple instrument known as Patient Health Questionnaire (PHQ). Those who screen positive may be further analyzed by nine item PHQ. However, culturally sensitive screening instruments have been devised across geographical boundaries which are sensitive and valid. Routine use of such instruments even in busy settings yields rich dividends. Although most of these instruments can be easily administered and scoring is also easy, the authors recommend that any one standardized instrument may be used to screen CAD patients for depression. If the patient tests positive, then depending on the situation and available resources detailed assessment by a psychiatrist may be undertaken. Even if such a facility does not exist and the patient is unwilling for a formal psychiatric referral, then at least a note of his symptoms must be made during follow-up. If the condition deteriorates or the functioning as well as QOL remains poor, then review of the case should be done in consultation with the psychiatrist.[38]

In last two decades more than 60 prospective studies have examined the link between depression, anxiety, QOL and PCI in patients with CAD [Tables 3-5]. The prevalence of anxiety in PCI patients varied 23.5%–66.5%. The prevalence of depression varied from 23% to 48%. Women have significantly higher prevalence of depression than men before and after PCI. Anxiety and depression levels were positively correlated to severity of CAD. The levels of anxiety and depression declined after PCI while QOL levels improved after PCI. HRQOL is negatively correlated with mental distress and continued smoking.

Table 3

Summary of studies assessing anxiety after percutaneous coronary artery intervention

Country Author	Patients and rating scale	Results	Conclusions
Netherland Pedersen et al. 2006[39]	692 patients 6 and 12 months After PCI HADS	471 (68.1%) had no symptoms of anxiety or depression, 62 (9.0%) had anxiety only, 59 (8.5%) had depressive symptoms only, and 100 (14.5%) had co-occurring symptoms	PCI patients with co-occurring anxiety and depression reported poorer health status compared with anxious/depressed only and no-symptom patients. Anxiety had incremental value to depressive symptoms in identifying those at risk for impaired health status
Iran Dehdari et al., 2008[40]	75 PCI and 75 CABG patients STAI	State anxiety 45.1±10.4 Trait anxiety 45.3±10.4	PCI patients had significantly higher anxiety as compared to CABG patients
India Chaudhury and Srivastava 2013[41]	35 patients assessed before and 3 days after PCI HADS	Anxiety at baseline 12.7±2.3 was significantly >3 days after PCI 6.1±1.5	Successful PTCA resulted in significant reduction in anxiety
Brazil Furuya et al., 2013[42]	59 patients assessed 2-7 months after PCI HADS	Anxiety found in 66.7% men and 56.3% women	No significant difference in men and women regarding anxiety
Austria Sipötz et al., 2013[43]	163 PCI patients HADS after intervention and at 1,6,12 and 24 months	HADS - score decreased significantly from baseline to 1-month follow-up only	Mental distress declined in 1st month of follow-up. MHRQOL is negatively correlated to mental distress
Turkey Ekici et al., 2014 [44]	225 PCI patients divided in to 3 groups: Normal coronary arteries (Gensini score 0, n=78, control group), minimal CAD (Gensini score 1-19, n=54), and significant CAD (Gensini score ≥20, n=93) HADS	Anxiety scores Control group=6.0 (3.5-9.0); Minimal CAD=7.0 (4.0-9.0); significant CAD=7.0 (4.0-11.0); P=0.459 (non significant)	A significant positive correlation was found between HADS-anxiety and Gensini scores (r=0.139, P=0.038)
Iran Moattari et al., 2014[45]	Experimental group (n=40) underwent a 12 weeks angina plan intervention consisting of 30 minutes counseling interview and telephone follow up. HADS at pretest and 3 months after PCI	Anxiety scores: Experimental group: Pretest 7.72±2.27; 3 months after PCI 6.57±1.72; Control group: Pretest 5.85±2.14; 3 months after PCI 5.92±2.30	Mean changes between two groups was significant
Iran Sharif et al., 2014[46]	Experimental group (n=40) participated in a 30-min training session before and after PTCA. The control group (n=40) received routine oral instructions before and after PCI. Both groups received an informative pamphlet at discharge. DASS on admission, at discharge, and 1 month after discharge	Anxiety scores Experimental group: T1=4.02±2.95; T2=3.40±2.83 T3=1.60±2.42 Control group: T1=4.12±3.09; T2=4.20±3.15; T3=4.82±3.51 Experimental group T1-T3 P<0.001 Experimental group T3-Control group T3 P<0.001	A planned discharge program in patients undergoing PTCA lowered their anxiety
Poland Uchmanowicz and Łoboz-Grudzień 2015[47]	90 patients (55 men, 35 women) aged 39-84 undergoing coronary angioplasty. STAI in first week, after 6 months and 36 months	Changes in the levels of anxiety as a state and anxiety as a trait showed an unfavorable trend: STAI-state: 28.5 in the first week versus 34.3 in the 36th months (P<0.001); STAI-trait: 30.0 in the first week versus 33.9 in the 36th months (P<0.001)	More attention should be paid to anxiety accompanying CAD. There is a relationship between HRQOL and sex, age, anxiety and depression
China Lv et al., 2016[48]	75 anxiety and depression patients after PCI randomly divided into CBT group (n=38) and control group (n=37) HAMD, HAMA, Chinese version, before, 3 days, and 8 weeks after PCI	HAM A scores in treatment and control group Before treatment was (23.3±7.9 and 24.2±8.1; P=0.62) which decreased to (10.6±3.4 and 16.5±4.6; P=0.003) respectively after 8 weeks	HAM-A scores were decreased after treatment, but were more substantially reduced in patients that underwent CBT than those in the control group
Iran Pournaghash-Tehrani and Abdoli-Bidhendi 2016[49]	90 patients undergoing PTCA. DASS 21 1 day before and 2 months after PTCA	There was a significant reduction of anxiety from pre PTCA to post PTCA in men (11.32±3.84-8.20±3.25) and women (11.06±3.62-7.19±3.20) respectively	PTCA was associated with improvement in anxiety of the patients
China Gu et al., 2016[50]	170 randomly selected CHD patients undergoing PCI. HADS 1 day prior and after PCI, and at 1,3,6 and 12 months after PCI	PCI significantly associated with anxiety, and comorbid anxiety and depression (χ2=90.18, 64.83; P<0.01) at each follow-up	Anxiety, and comorbid anxiety and depression significantly increases 1 day before and after PCI; but significantly decreases with time following PCI
Netherland Delewi et al., 2107[51]	2604 patients undergoing coronary angiography/PCI were included, with 70.4% male participants with a mean age of 65±12 years. VAS anxiety score at hospital intake, pre- and post-procedure, and at hospital discharge	At hospital intake the mean VAS anxiety score was 40.6±25.7. Mean preprocedural score was 43.9±26.8 and significantly declined postprocedure to 25.8±25.6 (P<0.001). The VAS anxiety score at hospital discharge was 19.5±21.7	Female patients had significantly higher preprocedure VAS anxiety score (50.4±26.5) compared to males (41.5±26.8, P=0.02). Other factors associated with higher levels of anxiety were age <65 years, low level of education and an acute primary PCI
Colombia Della-Méa et al. 2018[52]	266 patients who had undergone PCI; 68% men; average age 64.5 years (SD=8.9 years); beck anxiety inventory after PCI	26.3% patients had minimal anxiety; 22.2% mild anxiety; 21.8% moderate anxiety; and 29.7% had severe anxiety	Assessing and treating psychological symptoms after PCI may improve patient’s adherence to treatment and their QOL
Norway Olsen et al., 2018[53]	775 patients undergoing first time PCI at baseline and at 3 years follow up HADS	27% of patients undergoing PCI reported symptoms of anxiety (score≥8 on HADS)	After 3 years, patients had higher level of anxiety than the reference population. Female gender and young age are associated with anxiety

HADS – Hospital Anxiety and Depression Scale; STAI – Speilberger State trait anxiety inventory; DASS – Depression Anxiety Stress Scale; PCI – Percutaneous coronary artery intervention; CAD – Coronary artery disease; PTCA – Percutaneous transluminal coronary angioplasty; SD – Standard deviation; VAS – Visual Analogue Scales; CHD – Coronary heart disease; QOL – Quality of life; HRQOL – Health – related quality of life MHRQOL – MacNew HRQOL; CABG – Coronary Artery Bypass Graft; CBT – Cognitive behaviour therapy; HAMD – Hamilton depression rating scale; HAMA – Hamilton anxiety rating scale

Table 5

Summary of studies assessing health related quality of life after percutaneous coronary artery intervention

Country Author	Patients and rating scale	Results	Conclusions
Germany Kähler et al., 1999[54]	Patients aged 80 years or above (n=34) and youngerpatients (n=34) interviewed immediately after and 6 months after PCI with SF 36	Significant increase in theparameters RP from 29±8-61±15 (≥80) versus 26±7-46±16 (<80) and in bodily painfrom 44±16-71±22 (≥80) versus 40±19-57±29 (<80). The increase in the RP score after 6 months in the group ≥80 was significantly stronger than in the <80 group	PCI increases physicalabilities and decreases pain significantly more in octogenarians compared to younger patients with symptomatic coronary heart disease
Netherland Pedersen et al., 2006[39]	692 patients 6 and 12 months after PCI HADS SF 36	471 (68.1%) had no symptoms of anxiety nor depression, 62 (9.0%) had anxiety only, 59 (8.5%) had depressive symptoms only, and 100 (14.5%) had co-occurring symptoms. There was an overall significant improvement in health status between 6 and 12 months post-PCI	Patients with co occurring symptoms of anxiety and depression had poorer health status compared with anxious/ depressed only and no symptom patients. Anxiety has incremental value to depressive symptoms in identifying patients at risk for impaired health status
Poland Dudek et al., 2007[55]	156 patients with optimal PCI results SF 36	SF score 1 day before PCI=45.43±14.75 1 month after PCI=59.24±14.47 6 months after PCI=55.15±16.70 12 months after PCI=55.82±15.75	QOL before PCI was significantly lower than after PCI. QOL 6 months after PCI was significantly worse than at 1 month after PCI
Slovakia Škodová et al., 2011[56]	37 patients age <75 sinter viewed before and 1-2 years after PTCA. GHQ 28 and SF 36	Physical and mental component of HRQOL scores at baseline 45.8±20.6 and 56.6±18.5 was significantly less than at follow up 57.7±23.4 and 62.1±19.4	Improvement in physical HRQOL was predicted by baseline psychologic well-being and baseline HRQOL. Improvement in mental HRQOL was predicted by baseline psychologic well-being
India Chaudhury and Srivastava 2013[41]	35 patients assessed before and 3 days after PCI with EQ5D	On EQ5D health status score At baseline 42.7 (15.3) was significantly <3 days after PCI 78.7 (8.3)	Successful PTCA resulted in significant reduction in HRQOL
Austria Sipötz et al., 2013[43]	163 PCI patients MHRQOL after intervention and at 1,6,12 and 24 months	The comparison of baseline MHRQOL Global scores to the four points of follow-up showed, that clinically relevant improvement (≥0.5) occurred in 48.5-55.8% of the patients	MHRQOL improved up to 6 months after PCI. Mental distress declined during the first month after PCI. MHRQOL is negatively correlated to mental distress
Turkey Ekici et al., 2014[44]	225 patients undergoing elective PCI divided into 3 groups according to their Gensini score: normal coronary arteries (Gensini score0, n=78, control group), minimal CAD (Gensini score 1-19, n=54), and significant CAD (Gensini score ≥20, n=93) NHP	Total NHP scores Control group=109.2 (54.3-198.7) minimal CAD=138.4 (103.9-245.8) significant CAD=154.5 (63.3-298.8) P=0.059 (Not significant). The control group had significantly lower NHP-E and NHP-PM scores than the other groups (P=0.048, P=0.021, respectively)	A significant positive correlation was found between NHP-total score and Gensini scores (r=0.145, P=0.029)
Iran Sharif et al., 2014[46]	The experimental group participated in a 30-min training session before and after PTCA. The control group received routine oral instructions before and after angioplasty. At discharge, both groups received an informative booklet. DASS on admission, at discharge, and 1 month after discharge	Stress scores Experimental group: T1=6.82±4.45; T2=6.40±4.22; T3=3.57±3.50; Control group: T1=8.12±4.42; T2=8.20±4.58; T3=9.55±5.41; Experimental group T1-T3 P<0.001; Control group T1-T3 P<0.001 Experimental group T3-Control group T3 P<0.001	A planned discharge program in patients undergoing PTCA lowered their stress
Iran Moattari et al., 2014[45]	Experimental group (n=40) underwent a 12 weeks angina plan intervention consisting of 30 min counseling interview and telephone follow up at the end of 1,4,8 and 12 weeks. SAQ at pretest and 3 months after PCI	A significant change between the groups in the perception of QoL dimension of SAQ	No significant difference in the other dimensions of the QoL
India Tumkur et al., 2014[57]	75 patients treated with PTCA. EQ5D before PCI and after 1 month	HRQOL before angioplasty 0.462; 1 month after 0.6957 (P<0.001)	Improvement in QOL was highly significant
USA Jang et al., 2015[58]	2765 patients PCI classified as persistent smokers (n=315), quitters (n=189), past smokers (n=1326) or never smokers (n=935) on the basis of their smoking status at baseline. SF 36 and EQ5D VAS at baseline and 1 year follow up	Persistent smokers reported significantly lower SAQ angina frequency, physical limitation, QOL, and EQ-5D VAS scores when compared with never smokers at 1-year follow-up. Quitters had significantly better angina control and higher QOL scores than persistent smokers	HRQOL benefits of PTCA are diminished by continued smoking. Efforts to promote smoking cessation at the time of PTCA may substantially improve the health outcomes
Iran Pournaghash-Tehrani and Abdoli-Bidhendi 2016[49]	90 patients undergoing PTCA. SF 36, DASS21 1 day before and 2 months after PTCA	Stress and QoL had an inverse significant relationship. No significant relationship between anxiety and depression and QoL	PTCA was associated with improvement in QOL of the patients Systematic review and meta-analyis
Takousi et al., 2016[59]	Thirty-four longitudinal studies; included 8,027 patients who underwent PCI, 6,348 had CABG and 1,617 on medication only	Moderate long-term effect sizes were revealed for both PTCA and CABG. Both interventions had significantly greater effects on HRQoL than medication; the CR procedures did not differ significantly from each other	Benefits related to physical functioning were greater than those related to psychosocial functioning in patients treated with CABG
India Singh et al., 2020[60]	30 patients each of CABG and PTCA at baseline and 6 months with WHO-QOL BREF	Scores of WHO QOL BREF were 2.5±0.63 and 3.0±0.78 in PTCA group and 2.7±0.97 and 3.1±0.84 in CABG group	Controlling for hypertension, diabetes mellitus and postintervention diet restriction CABG predicted lower improvements in overall QoL compared to PTCA

HADS – Hospital Anxiety and Depression Scale; SF 36 – Short form; GHQ – General Health questionnaire; QOL – Quality of life; EQ5D – Euro QOL questionnaire; HRQOL – Health related QOL; MHRQOL – MacNew HRQOL; WHO-QOL BREF – The World Health Organization QOL assessment Brief; NHP – The Nottingham health profile; DASS – Depression Anxiety Stress Scale; SAQ – Seattle angina questionnaire; CR – Coronary revascularization; RP – Role physical; PTCA – Percutaneous transluminal coronary angioplasty; CAD – Coronary artery disease; VAS – Visual Analogue Scales; CABG – Coronary artery bypass graft; PM – Physical mobility

Case vignette

Fifty-four-year-old service officer reported with a history of angina. He had been smoking one packet of cigarette per day for the last 15 years. His mother had died of heart attack at the age of 65 years. Initial cardiac workup revealed triple vessel disease with ejection fraction of 32%. On specific interview, he revealed his worries about his health but denied any history of persistent pervasive sadness, anhedonia, hopelessness or suicidal thoughts. The patient underwent PCI with drug-eluting stenting on two coronary arteries. The procedure was uneventful. He was discharged on clopidogrel 75 mg OD, Tab Atorvastatin 20 mg OD. When he reported for review at the end of 6 weeks, he complained of early morning sadness which persisted till about afternoon. He also complained of vague generalized body pain which was worse in the mornings. He developed a belief that that he will soon die of heart attack. He experienced repeated awakening from sleep in the night. His appetite was poor and he had lost all interest in sexual activity with his wife. He also revealed experiencing palpitations and restlessness intermittently lasting about 15 min on most days for no apparent reason. An interview with his wife revealed that he had become irritable and did not enjoy his favorite TV program or reading newspaper which he did earlier. He expressed unwillingness to rejoin his duty citing high stress and his inability to cope. He sought specific recommendation regarding change in his duties. He was prescribed a hypnotic agent, Tab Alprazolam 0.25 mg at bed time which improved his sleep in that the frequent awakenings diminished by about 75% over 1 week. However, he felt miserable in the mornings with feeling of profound fatigue and malaise. He had to force himself out of bed and for routine daily chores. Now he had frequent crying spells while he interacted with his family members and friends. Their support and reassurance that his heart problem was well under control did not help to improve his overall condition. When the cardiologist offered a psychiatric referral, he felt offended and vehemently opposed the idea and claimed that he had been a high achiever all his life and had not become mad to visit a psychiatrist. Screening on PHQ-9 revealed that he had little interest in doing things, feeling depressed, poor appetite, trouble concentrating and easy fatigability on most of the days since past few weeks. He believed that he had become a burden on the family and the organization (Items 1, 2, 4, 5, 6, 7 and 8 on PHQ-9). After an expert counseling by the cardiologist, patient finally agreed to see a psychiatrist. After about 03 weeks of treatment which included both supportive psychotherapy and Tab Sertraline 50 mg per day, patient regained his confidence to rejoin duties. His mood lifted and his energy levels became almost normal. The feeling of being a burden on the family and the organization did not persist any longer.

MANAGEMENT ISSUES

It is prudent if cardiologists screen all CAD patients for depression. However, in India, such an assessment system is still in its infancy.[10] An informal interaction with prominent cardiologists at three reputed coronary care units (two government and one corporate sector) revealed that referral to psychiatrist was rare. However, cardiologists at all three centers acknowledged the high prevalence of somatic complaints among their clientele which may have been due to underlying psychiatric illness.[61] One such study in one of these centers found that 46% had significant anxiety and 32.1% had significant depression before PTCA though there was significant reduction of both depression and anxiety following successful PTCA.[41] Therefore, it is important to screen for depression, overcome barriers and treat systematically as the illness has significant influence on treatment adherence, rehabilitation and QOL.[23] Manifestation of depression following PCIs is likely to be missed especially in younger patients as their symptoms might be interpreted as seeking secondary gain.[62] The issue is sensitive and may require expert handling and may affect doctor patient relationship. However, the setting of treatment and the underlying principles of management may govern the kind of intervention as well as follow up and disability certification in such cases.

PLANNING AN INTERVENTION

Holistic assessment, early diagnosis and intervention in CAD patients have not only economic but also social benefits. The issue gains further importance in third world countries where resources in public sector are scarce and not evenly distributed. Corporate sectors, though proclaiming high quality medical care often fall much short of providing holistic care and work on package system where patients are treated like commodities.[6364] Delivery of psychosocial intervention is difficult to define and measure which complicates its evaluation for efficacy. Total cost rendered for such interventions also need to me monitored as its gains must be commensurate with the efforts and cost.[65] Therefore, a systematic approach towards following queries will assist the clinician in formulating plan for intervention:

How much is the severity of symptoms and is it interfering with routine daily activities (individual, family, occupational, or socially)?

Are the patient and his family members convinced about the need for psychiatric intervention?

Are there any clear benefits in offering psychiatric intervention and is follow up viable?

Enhancing Recovery in Coronary Heart Disease patients (ENRICHD) trial was the first such multicenter intervention for depression and psychosocial adversity following myocardial infarction (MI).[66] Key features of the intervention included integration of cognitive behavior and social learning approaches for treatment of depression and diverse set of problems that can contribute to low social support after MI. ENRICHD intervention resulted in reduced depression and increased social support, especially during the first 6 months. However, it did not have much impact on overall mortality figures.

The authors of this article recommend routine screening for depression in patients suffering from CAD using a simple screening instrument like PHQ-2. Those who score positive on both the items should be screened with depression screening instrument like Hospital Anxiety and Depression Scale.[6567] If the score is below the cut-off then the patient should be educated about depression as an illness. In case there is past history of mood disturbance or a family history of a psychiatric illness or suicide, or the score is above the cut-off the patient should ideally be handled by a psychiatrist. However, routine follow up may continue by the primary care physician. There are multiple other modalities cutting across cultures proclaiming benefits and even reversal of CAD but data provided lacks consistency.[686970] The results are difficult to replicate in view of inherent complexities of its methods, patient participation and the way results are tabulated and reported. There are views and counterviews of these methods but supervised regular cardiac exercises have consistently proved to be effective in improving cardiac status.[717273] Cardio activities include yoga, aerobics, walking, jogging, cycling, skipping, dancing and swimming. Exercise training in patients with CAD increases exercise capacity, reduces cardiac ischemia, delays the onset of or eliminates angina and improves endothelial function thereby leading to reduced mortality rates.[74] Quitting smoking is the most effective intervention to reduce mortality in patients with CAD. There are effective treatments available for nicotine dependence though continuity of care is important. Hospitalization for CAD provides an important opportunity to intervene with smokers when their motivation to quit is high. Posthospitalization quit rates should be a benchmark of cardiac program performance.[7576] Rightful choice of psychotherapy and pharmacotherapy can be made after consultation with an expert.

CONCLUSION

CAD remains an anathema of the physician and is the world's biggest killer. Depression, anxiety, and psychosocial issues are inherently ingrained in the complex web of the development and progression of CAD and innumerable studies have highlighted the importance of their recognition at various stages of the illness. There are significant gains to be made if such issues are addressed in a timely and systematic manner. The authors recommend regular screening by simple and culturally sensitive instruments. Mild to moderate severity cases can be addressed by the cardiac care team but severe cases must be referred for expert intervention. There is insufficient data to recommend psychosocial interventions but attempts must be made if gains outweigh the costs. Graded and supervised cardiac exercise and smoking cessation programs besides counseling for weight and diet management can go a long way in promoting cardiac health and must be integral to any cardiac care facility.

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Conflicts of interest

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Table 4

Summary of studies assessing depression after percutaneous coronary artery intervention

Country Author	Patients and rating scale	Results	Conclusions
Netherland Pedersen et al., 2006[39]	692 patients 6 and 12 months after PCI HADS	471 (68.1%) had no symptoms of anxiety nor depression, 62 (9.0%) had anxiety only, 59 (8.5%) had depressive symptoms only, and 100 (14.5%) had co-occurring symptoms	Patients with co-occurring anxiety and depression reported poorer health status compared with anxious or depressed only patients and no-symptom patients. Anxiety has incremental value to depressive symptoms in identifying PCI patients at risk for impaired health status
Poland Dudek et al., 2007[55]	156 patients with optimal PCI result Depression=HDRS21 >10/BDI >11	75 (48.1%) patients had depression before PCI which persisted in 38 Patients 1 month after PCI. 81 (51.9%) patients did not have depression before PCI but 12 of them were depressed 1 month after PCI	No significant correlations between cardiovascular function impairment (CCS criteria) and severity of depressive symptoms
India Chaudhury and Srivastava, 2013[41]	35 patients assessed before and 3 days after PCI with HADS	Depression at baseline 11.4 (2.7) was significantly >3 days after PCI 7.2 (1.9)	Successful PTCA resulted in significant reduction in depression
Brazil Furuya et al., 2013[42]	59 patients assessed 2-7 months after PCI HADS	Depression found in 14.8% men and 43.7% women	Women had significantly higher prevalence of depression compared to men
Austria Sipötz et al., 2013[43]	163 PCI patients HADS after intervention and at 1,6,12 and 24 months	HADS-Total score decreased significantly from baseline to 1 month follow-up (P=0.02). No significant change thereafter	Mental distress declined during the first month of the follow-up period. MacNew HRQOL is negatively correlated to mental distress
Turkey Ekici et al., 2014[44]	225 patients undergoing elective PCI divided into 3 groups as per their Gensini score: normal coronary arteries (Gensini score 0, n=78, control group), minimal CAD (Gensini score 1-19, n=54), and significant CAD (Gensini score ≥20, n=93); HADS	Depression scores: Control group=4.0 (2.0-6.5) Minimal CAD=5.0 (3.0-7.5) Significant CAD=5.5 (3.0-9.0) P=0.322 (Not significant)	A significant positive correlation was found between HADS-anxiety and Gensini scores (r=0.156, P=0.019)
Iran Moattari et al., 2014[45]	Experimental group (n=40) underwent a 12 weeks angina plan intervention consisting of 30 min counseling interview and telephone follow up at the end of 1,4,8 and 12 weeks. HADS at pretest and 3 months after PCI	Depression scores experimental group: Pretest 5.92±2.65; 3 months after PTCA 5.52±3.13 Control group: Pretest 4.90±2.91; 3 months after PTCA 4.77±2.61	Mean changes between two groups was not significant
Iran Sharif et al., 2014[46]	Experimental group participated in a 30-min training session before and after PTCA and an informative booklet at discharge. Control group received routine oral instructions before and after angioplasty and an informative pamphlet at discharge DASS on admission, at discharge, and 1 month after discharge	Depression scores Experimental group T1=5.00±3.44; T2=4.45±3.31; T3=2.45±2.49 Control group: T1=4.85±3.02; T2=4.97±3.04; T3=5.95±3.76 Experimental group T1-T3 P<0.001 Experimental group T3-control group T3 P<0.001	A planned discharge program in patients undergoing PTCA lowered their depression
Poland Uchmanowicz and Łoboz-Grudzień 2015[47]	90 patients (55 men, 35 women) aged 39-84 undergoing coronary angioplasty. BDI in first week, after 6 months and 36 months	An analysis of the dynamics of changes in the severity of depressive symptoms according to the BDI shows an increase from 4.6 in the first week to 10.4 points in the 36th month (P<0.001)	More attention should be paid to depression after PCI to improve QOL
China Lv et al., 2016[48]	75 anxiety and depression patients after PCI randomly divided into CBT group (n=38) and control group (n=37). HAMD, HAMA, Chinese version, before, 3 days, and 8 weeks after PCI	HAM D scores in treatment and control group before treatment was (19.5±6.8 and 19.0±7.9, P=0.77) which decreased to (11.7±4.5 and 15.1±3.9; P=0.001) respectively after 8 weeks	HAM-A scores were decreased after treatment, but were more substantially reduced in patients that underwent CBT than those in the control group
Iran Pournaghash-Tehrani and Abdoli-Bidhendi 2016[49]	90 patients undergoing PTCA. DASS 21 1 day before and 2 months after PTCA	There was a significant reduction of depression from pre PTCA to post PTCA in men (12.86±3.66-9.18±3.32) and women (12.26±4.18-8.60±3.42) respectively	PTCA was associated with improvement in depression of the patients
China Gu et al., 2016[50]	170 randomly selected CHD patients undergoing PCI. HADS 1 day prior and after PCI, and at 1,3,6 and 12 months after PCI	PCI significantly associated with depression, and comorbid anxiety and depression (χ2=54.45, 64.83; P<0.01) at each follow-up	Depression, and comorbid anxiety and depression significantly increases 1 day before and after PCI; but significantly decreases with time following PCI
Colombia Della-Méa et al., 2018[52]	266 patients who had undergone PCI; 68% men; average age 64.5 years (SD=8.9 years); Beck depression inventory II after PCI	51.9% patients had minimal depression; 25.9% mild depression; 12.8% moderate depression; and 9.4% patients had severe depression	Assessing and treating psychological symptoms after PCI may improve patient’s adherence to treatment and their QOL
Norway Olsen et al., 2018[53]	775 patients undergoing first time PCI at baseline and at 3 years follow up HADS	27% and 19% of patients undergoing PCI reported symptoms of anxiety and depression	After 3 years, patients had higher level of anxiety, but not depression, than the reference population. Older age, lower-education and previous cardiovascular morbidity are associated with depression

HADS – Hospital Anxiety and Depression Scale; DASS – Depression Anxiety Stress Scale; HDRS – Hamilton depression Rating; Scale; BDI – Beck depression inventory; PCI – Percutaneous coronary artery intervention; CAD – Coronary artery disease; PTCA – Percutaneous transluminal coronary angioplasty; CHD – Coronary heart disease; QOL – Quality of life; HRQOL – Health related QOL; MHRQOL – MacNew HRQOL; CBT – Cognitive behaviour therapy; CCS – Canadian cardiovascular society; HAMD – Hamilton depression rating scale; HAMA – Hamilton anxiety rating scale