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https://doi.org/10.47803/rjc.2020.30.1.35

Márta Germán-Salló1,2, Zoltán Preg1,2, Enikő Nemes-Nagy3, Dalma Bálint-Szentendrey1,2, Tünde Pál4, Károly Csomay1

1 „George Emil Palade” University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania
2 Department of Cardiovascular Rehabilitation, Emergency Clinical County Hospital, Targu Mures, Romania
3 Department of Fundamental Pharmaceutical Sciences, „George Emil Palade” University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania
4 Emergency Institute for Cardiovascular Diseases and Transplantation, Targu Mures, Romania

Abstract: Objectives – To investigate the prevalence of psychosocial risk factors (PRFs) among patients admitted to a cardiovascular rehabilitation clinic. Methods – 431 consecutive inpatients were included. Baseline characteristics and clinical data were extracted from clinical charts. We applied the European Society of Cardiology (ESC) standardized psycho-social questionnaire. Patients were asked about socio-economic status, including education level, work and family stress, social isolation, depression, anxiety, hostility, type D personality, post-traumatic stress disorder, other mental disorders. Results – The mean age was 68±10 years, with female predominance (51.7%). The most common cardiovascular risk factor was hypertension (94.7%), mean blood pressure was 136/81 mmHg (±20/11 mmHg). The most frequently observed PRFs were social isolation (72.2%), low socio-economic status (63.8%), work stress (65.2%) and hostility (65.9%). Social isolation (p=0.0034), depression (p<0.0001), anxiety (p<0.0001), hostility (p=0.0438), type D personality (p<0.0001), post-traumatic stress disorders (p=0.0004) and other mental disorders (p=0.0350) were more frequent in women. Men suffered signifi-cantly more frequent from work stress (p= 0.0409). Conclusions – PRFs are common among patients with CVD with significant gender differences. Screening for PRFs can easily be performed. Identification of affective disorders and other chronic stressors may have an impact on future cardiovascular events and on treatment adherence. Keywords: cardiovascular diseases, psychosocial risk factors, cardiovascular prevention, classical risk factors.
Rezumat: Obiectiv – Evaluarea prevalenţei factorilor de risc psihosociali într-o clinică de recuperare cardiovasculară. Metode – Am inclus consecutiv 431 de pacienţi internaţi în această clinică. Caracteristicile de bază şi datele clinice au fost extrase din foile de observaţii. Am utilizat chestionarul psiho-social standardizat, recomandat de Societatea Europeană de Cardiologie. Pacienţii au fost chestionaţi asupra statusului socio-economic, inclusiv nivelul de educaţie, stresului de la servici şi în viaţa de familie, lipsei de sprijin social, depresiei, anxietăţii, ostilităţii, personalităţii de tip D, stresului post-traumatic şi asupra altor afecţiuni psihiatrice. Rezultate – Vârsta medie a fost de 68 ±10 ani, cu predominanţa femeilor (51,7%). Cel mai frecvent factor de risc cardiovascular a fost hipertensiunea arterială (94,7%), tensiunea arterială medie a fost 136/81 mmHg (20/11 mmHg). Factorii psihosociali cei mai des întâlniţi în studiul nostru au fost absenţa sprijinului social (72,2%), statusul socio-economic precar (63,8%), stresul ocupaţional (65,2%) şi ostilitatea (65.9%). Absenţa spirjinului social (p=0,0034), de-presia (p<0.0001), anxietatea (p<0,0001), ostilitatea (p=0,0438), personalitatea de tip D (p<0,0001), stresul post-traumatic (p=0,0004) şi alte afecţiuni psihiatrice (p=0,0350) au fost mai frecvent întâlnite la femei. Bărbaţii au fost mai des expuşi stresului ocupaţional (p=0.0409). Concluzii – Factorii de risc psihosociali sunt frecvent prezenţi la pacienţii cu boli cardio-vasculare existând diferenţe semnifi cative între sexe. Screeningul lor se poate efectua cu uşurinţă. Identificarea tulburărilor afective şi a altor stresori cronici psihosociali pot avea un impact asupra dezvoltării, prognosticului bolilor cardiovasculare şi asupra aderenţei la tratament.
Cuvinte cheie: boli cardiovasculare, factori de risc psihosocial, prevenţie cardiovasculară, factori de risc tradiţionali.

List of abbreviations used in text
CVD    cardiovascular disease
ESC       European Society of Cardiology
PAD     peripheral artery disease
CHD    coronary heart disease
PRFs    psychosocial risk factors
HTN    arterial hypertension
SBP        systolic blood pressure
DBP     dyastolic blood pressure
BMI        body mass index
MI          myocardial infarction
CABG coronary artery bypass graft
PCI        percutaneous coronary intervention
BDI-13 Beck Depression Inventory-13 item form
PTSD    post-traumatic stress disorder

INTRODUCTION
The prevalence of cardiovascular diseases (CVD) according to a survey which included member coun-tries of the European Society of Cardiology (ESC) was approximately 83.5 million in 20151. Peripheral artery disease (PAD) was at the top of the list (35.7 million) followed by coronary heart disease (CHD) (29.4 milli-on)1. CVD are the leading cause of mortality and mor-bidity, being responsible for around 45% of all deaths in Europe2, with a higher mortality rate in Central and Eastern Europe2. Data suggest, no change is predicted in the near future, due to the aging and growing of the population. There is a worldwide variation in the inci-dence CVD with a higher burden in low and middle-income countries3.
Traditional risk factors do not fully explain the CVD risk in populations, and there is increasing awareness of the impact of social environment and psychological factors on CVD incidence and outcomes. The measu-rement of psychosocial variables is uniquely complex as variables are difficult to define objectively4. Risk fac-tors related to an increased risk of development of CVD were firstly mentioned in studies derived from the Framingham Heart Study5. High blood pressure and high cholesterol level were found to be associated with cardiovascular risk and outcomes6. Additionally, the same study, demonstrated the promoting role of other risk factors in cardiovascular diseases, like di-abetes mellitus, smoking, physical inactivity and obe-sity5. These are recognized as classical cardiovascular risk factors. Cardiovascular disease mostly develops in those who are exposed to at least one of these hazards. Noteworthy, they are easily quantifi able and infl uencing them has been for a long time the core action in cardiovascular prevention and rehabilitation.
Lately, besides traditional cardiovascular risk fac-tors, the role of individual psychosocial risk profile in CVD development came into the spotlights. Emer-ging data show the causative or intermediate effect of psychosocial risk factors (PRFs), classified as emotio-nal factors such as depression, anxiety, anger, hostility and chronic stressors including low socioeconomic status, low social support, work stress, marital stress and caregiver strain7-9 in relationship with CVDs. The role of PRFs in cardiovascular diseases mainly was in-vestigated in relation with the burden and prognosis of coronary heart disease10-12, heart failure and arrhyth-mias13. In a recent review Rozanski reports, that des-pite this growing knowledge, translation into clinical cardiology did not become a practice14.
The current 2016 European Guidelines on CVD prevention tries to overcome this problem. According to it, assessment of PRFs could be important, as these play a role in the development and prognosis of CVD and also have an impact on lifestyle and treatment adherence15. The use of standardized questionnai-res or clinical interviews should be considered (class of recommendation IIA; level of evidence B) in high CVD risk patients based on total CVD risk assessed by SCORE chart or in patients already diagnosed with CVD15. Currently, there is insufficient data to support the routine assessment of these factors15. However, there is growing evidence, that psychosocial risk profi le identifi cation may have positive influence on cardiovascular disease progression. In any case, des-pite recommendations, implementation of guideline is frequently lacking in everyday practice.
The aim of this study was to investigate psycho-social risk factors among patients in a cardiovascular rehabilitation clinic. Using a standardized questionna-ire proposed by ESC prevention team, we also try to show, that implementation of guidelines recommenda-tions is achievable15.

METHODS
This cross-sectional study was conducted at the Târgu Mureş Cardiovascular Rehabilitation Department. A total number of 431 patients were included. All par-ticipants underwent general physical examination, height, weight and blood pressure measurement. We recorded socioeconomic and demographic data, clinical data including personal and family history of comorbidities and cardiovascular risk factors. Routi-ne laboratory investigations (complete blood count, glycaemia, full lipid profile, creatinine, uric acid, liver enzymes, and urine sample) were done in every pa-tient, as well as ECG and cardiac ultrasound. Other paraclinical investigations were completed according to each patient’s disease profile.
Each participant enrolled in the study fi lled in the standardized self-administered psychosocial questi-onnaire on mother tongue (Romanian or Hungarian). To be mentioned that this was administered irrespec-tive of the 10 year cardiovascular SCORE risk chart (this was evaluated only in patients with no manifest cardiovascular disease). The questionnaire consisted of nineteen items in nine topics: low socio-economic status (also one question with respect to education level, divided into six categories: 1st category (C): 1-4 classes, 2nd C: 5-8 classes, 3rd C: Gymnasium, 4th
C: Professional school, 5th C: Vocational school, 6th
C:University), work and family stress, social isolati-on, depression, anxiety, hostility, type D personality, post-traumatic stress disorder and other mental di-sorders15. This form is slightly extended compared to the version recommended in the 2012 European gui-delines on the prevention of CVD in clinical practice16. In addition most of patients completed the shortened 13-item form Beck Depression Inventory.
The Ethics Committee of the Emergency County Clinical Hospital of Targu Mures approved the study and patients signed a consent form to participate in our research study.
Microsoft Office Excel was used for data input and statistical software SPSS v.20.0 for data management and analyses. Descriptive statistics were performed for variables and expressed as mean ±SD and frequen-cy (%) for categorical variables.

RESULTS
The study analyzed data for 431 patients, ranged from 37 to 93 years, mean age 68±10 years. The majority of the participants were females 51.7% (n=223), 51.6% of patients came from rural environment. Most of them had attained gymnasium 24.0% (n=101) and classes from fi ve to eight 28.6% (n=120), a significant pro-portion of the participants had professional education 21.8% (n=94) and only 12.6% (n=53) had a university degree (Table 1).
The most common classical cardiovascular risk fac-tor was arterial hypertension (HTN) (already diagno-sed and treated or newly diagnosed), 94.7% (n=408) of the patients had different grades of HTN. The majority of the participants had second grade HTN 60.1% (n=259), and 74.5% (n=321) with very high additional cardiovascular risk. Overall mean blood pressure under antihypertensive therapy was 136/81 mmHg (±20/11 mmHg). Hypercholesterolemia was detected in 33.1% (n=143). Disorders in glucose ho-meostasis were observed in almost half of the cases 48.1% (n=207) with the predominance of type 2 dia-betes 38.3% (n=165). Obesity was present in 53.59% (n=231), the most common was grade one obesity 32.71% (n=141) and overall mean BMI was 31.05 ±6.11 kg/m2 and 29.5% (n=127) of the enrolled patients had normal weight (Table 2).
In our study, the most frequent psychosocial fac-tors were social isolation (72.2%), low socio-econo-mic status (63.8%), work stress (65.2%) and hostility (65.9%). Gender-related signifi cant difference was detected in the presence of psychosocial risk factors. Social isolation (p=0.0034), depression (p<0.0001), anxiety (p<0.0001), hostility (p=0.0438), type D per-sonality (p<0.0001), post-traumatic stress disorders (p=0.0004) and other mental disorders (p=0.0350) were more frequent by women. While men signi-ficantly more frequently suffered from work stress (p= 0.0409) compared to women. The prevalence of low socio-economic status and family stress did not differ between sexes in our study. Depression was present in 31.6%. However, after 83% of the pati-ents (n=359) completed the shortened 13-items form Beck Depression Inventory (BDI-13) this increased to 46.63% (n=201). Mild depression was present in 29.7% (n=128), moderate in 8.6% (n=37) and severe depres-sion in 8.4% (n=36) of the participants (Table 3).
Psychosocial stress factors usually appear in associ-ation with each other (Table 4). In this paper approx. in 17% from three to five psychosocial factors were present in the same individual.

DISCUSSION
Psychosocial risk factors are highly prevalent in car-diovascular illnesses. Emerging data suggest, they do have a role in the etiology of the disease, may promote progression and also could be a barrier to treatment adherence. The INTERHEART case-control trial (con-ducted in 52 countries) offers a larger perspective on the global evaluation of coronary artery disease risk factors10. The study concluded that nine cardiovascu-lar risk factors, including traditional cardiovascular risk factors completed with PRFs, are deemed for more than 90% of the risk for acute myocardial infarction10. Smoking and hyperlipidemia were the most strongly related to the acute event followed by psychosocial factors, abdominal obesity, diabetes and hypertensi-on11. Interestingly, current evidence from the literatu-re suggest, that PRFs may also have a role in promoting other major cardiovascular risk factors like hyperten-sion or diabetes mellitus4. The relationship between PRFs and stroke have been also largely evaluated in several studies, like Interstroke and Copenhagen City Heart Study, showing that risk of stroke is increased in the presence of psychosocial stressors10,17. Despite these findings, influence of PRFs on CVDs is still un-derestimated in comparison to traditional risk factors.
Therefore, integrating psychosocial risk profi le eva-luation into cardiology practice is becoming an urgent need. This study shows our experiences in the scree-ning of psychosocial risk factors. In comparison to tra-ditional cardiovascular risk factors these are less easily quantifiable and more subjective, as they are based on self-report. However, the standardized psychosocial risk assessment tool recommended by the ESC co-uld be easily administered in our patients admitted to the cardiovascular rehabilitation clinic. Based upon the answers obtained during the self-administered questionnaire we were able to identify affective disorders (depression, anxiety), personality traits (hostility, D-type personality) as well as chronic stressors like low socio-economic status, social isolation, marital and work related stress.
Low social status is measured by education degree and family income and it is related to the develop-ment of CHD18 and CHD mortality19 and also with poor prognosis in CVD20. More than half of our study population fell into the category of low social status. Family stress was less frequently encountered among our patients. In general population being unmarried, independently of gender, is related to a higher inci-dence of CHD and cardiac mortality21. Studies suggest that being married facilitates a healthy behavior and lifestyle, adherence to treatment, the recognition of symptoms in heart failure22.
Work stress including high job demands, low con-trol at work, long working hours are widely investiga-ted in CHD. According to a large meta-analysis, the-re is unequivocal association between job strain and CVD risk23. The largest case-control trial in this fi eld demonstrates that work stress is associated with a doubled risk of CHD and it is more important in men than in women11. Our results also show a significantly higher prevalence of work stress among men compa-red to women. Overall more than half of the inquired patients reported stress related to work. According to a recent cohort study, long working hours also in-crease stroke risk24.
Data from the literature are consistent regarding the association of depression and heart disease. Fu-ture projections of the WHO places depression as a second cause of disability in developed countries, just after CVDs25. Depression is considered an indepen-dent risk factor related to the incidence and prognosis of CHD26. It is also proved to be common among sur-vivors of acute cardiac events27. Patients with depres-sion are less likely to adhere to secondary preventive measures like quitting smoking, eating healthy or being physically active. The findings of the EUROASPIRE IV survey also support this statement and connect this negative emotional factor to other cardiovascular risk factors, such as current smoking, central obesity and diabetes28. Furthermore, as shown in a meta-analysis conducted by Pan and collaborators, depression is also linked to stroke risk29. We found depression in almost half of our patients, with a female predominance. Mild and moderate forms were more frequent. One third of the cases were revealed only, when Beck Depression Inventory was administered.
Besides depression, anxiety is another negative emotion proved to be an independent risk factor for CHD and cardiac mortality. This connection is less strong in comparison to the that of depression, on the other hand is stronger when compared to anger30. In our study prevalence of anxiety was comparable to that of depression and was also more frequent in women. Undoubtedly, the overlapping of anxiety and depression may strengthen the emotional distress of these individuals. Data from the national SWEDE-HEART registers showed that in patients after a myo-cardial infarction cardiovascular and general mortality are both increased if symptoms of anxiety and de-pression are constantly present31. With almost every second patient being anxious, our results showed a higher prevalence when compared to 30-40% found in a systematic review30. Evidently, the different anxiety evaluation method can explain this finding.
With respect to hostility and anger Chida and colla-borators stated in a meta-analytic review of prospecti-ve cohort studies, that these negative traits are linked to enhanced rate of events both in healthy subjects and those with established CHD30. Furthermore, they may increase the likelihood of recurrence30. Inte-restingly, connection of anger and hostility to CHD events was stronger in healthy men compared to wo-men32. Opposite to this, hostility was more frequent in our female patients. However, overall this was the second most prevalent psychosocial risk factor among our patients. Anger is also related to increased cardiac mortality and poor prognosis in patients with CHD32.
Type D personality defines a high level of negative thoughts and emotions. It appears in one-third of indi-viduals with CVD33. We demonstrated a much higher incidence, more than half of our patients confessed negative emotions, with female predominance.
Post-traumatic stress disorder (PTSD) is a reaction caused by a life-threatening event (like myocardial in-farction) making a person to become anxious, frighte-ned, helpless, frequently affecting his daily functioning. It is a negative emotional state in which individuals may re-live the traumatic event, avoid reminders and have negative thoughts and feelings. Prevalence of PTSD is high among patients with cardiac diseases, appears more frequently in women and is responsible for hi-gher mortality34. Our study is consistent with these findings, as we found PTSD in more than half of the patients, with female predominance.
The THORESCI study, a prevalence study in coro-nary heart disease patients from the Netherlands used the same questionnaire applied in our study showing a better psychosocial profile of their patients: social iso-lation 28% vs. 72%, depression 24% vs. 31.6%, hostility 53% vs. 65.9%, type D personality 50% vs. 55.5%, with a slightly less prevalent anxiety in our patients 48% vs. 45.2%35.
Psychosocial risk factors are often related to each other and their effects are cumulative which may in-crease the rate of cardiovascular events. The risk of CVD owed to the combination of these factors in some studies was similar to the risk associated to CHD traditional risk factors, such as hypertension, hypercholesterolemia36. For instance, chronic stress at work is related to increased incidence of depressi-on37, and both can promote ischemic heart disease38,39. Furthermore, low socioeconomic status was obser-ved to accompany social isolation and depression33. We observed in our study clustering of three to five PRFs which may enhance global health risk.
The association of traditional cardiovascular risk factors with PRFs was not evaluated in this work. However, according to the literature there is con-vincing data supporting the existence of a relations-hip between PRFs and traditional risk factors, such as hypertension, hypercholesterolemia, smoking, diabe-tes, obesity and physical inactivity13,34. For instance, in acute stressful events blood pressure increases tran-siently. Moreover, a higher incidence of hypertension associated with the presence of chronic stressors was observed, in particular if the stress managing respon-se was altered due to depression or anxiety40. Asso-ciation of PRFs with unhealthy behavior (sedentary lifestyle, alcohol and tobacco use, poor diet) is also well documented, as well as their negative influence on treatment adherence. Overall, a broad spectrum of biological, psychological and social variables, seem to act synergistically resulting in increased CV morbidity and mortality.
Cardiologist and general physician can easily take measures for the assessment of PRFs while taking medical history with simple questions or using stan-dardized questionnaires. In special cases, when it is necessary they need to refer the patient for further investigations and special treatment. Interventions to the decrease psychosocial hazard include individuali-zed recommendations regarding education, and phy-sical activity, promoting healthy behaviors, relaxation methods, stress management13,33. In special cases, like patients with clinically severe symptoms, psycho- and pharmacotherapy, coordinated by a specialist might be needed13. It is unanimously accepted that exercise is benefi cial for the prevention of CHD, but it was also demonstrated that may reduce the incidence of depression7.
The limitation of the present study includes that we did the research on consecutive inpatients, indepen-dently of the results of SCORE risk chart. In addition, a great proportion of enrolled patients were pensio-ners, a part of them missed to answer the following questions: „Are you a manual worker”; „Do you lack control over how to meet the demands at work?”; „Is your reward inappropriate for your effort?”, whi-ch imply bias on the interpretation of the first two psychosocial factors. Also, the results for depressive status are questionable, as the presence of depression according to the BDI-13 test was double compared to the prevalence obtained with the psychosocial ques-tionnaire. Furthermore, independent variables were not investigated in our study.
Besides focusing on traditional cardiovascular risk factors and their prevention, physicians should be aware of the presence and effect of novel cardiovas-cular risk factors, such as psychosocial domains. Early detection and treatment of emotional and behavioral disturbances may attenuate the incidence of CVD events, treatment adherence, and quality of life.

CONCLUSION
Overall, this paper presents the results of a survey on psychosocial risk factors among patients with CVD. The present findings confi rm that PRFs are common in patients with CVD and also suggest gender differen-ces in the prevalence of PRFs. Findings highlight the need to raise the awareness of these non-traditional risk factors and also show that screening for them can easily be performed. Further research is required to elucidate whether addressing these psychosocial at-tributes and integrating them in global cardiovascular risk assessment and cardiovascular rehabilitation pro-grams will be able to change the course of the CVD along the cardiovascular continuum.

Conflict of interest: none declared.

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