The Relationship of Biological and PsychologicalRisk Factors of Cardiovascular Disorders in a

Large-scale National Representative CommunitySurvey

Gy6rgy Purebl, MD; Emma Birkds; Csilla Csoboth, MD, PhD;Irena Szumska, PhD; Mdiria S. Kopp, MD, PhD

A large-scale national representative community survey qf 11,122 persons

aged more than 35 years included the investigation of the coincidence ofdepressive symptoms, vital exhaustion, cardiovascular disorders, stroke, andmyocardial infarction. A total of 20.3% of the survey participants reported

having experienced a cardiovascular disorder (CVD). Of the subjects report-ing a CVD, 52.1% exhibited depressive symptoms (22.0% subthreshold

depressive symptoms, 30.1% clinical depression), and 69.7% exhibited vitalexhaustion. The authors investigated 3 cardiovascular subgroups: (1) subjectshaving experienced a myocardial infarction (MI), (2) subjects having experi-enced stroke, and (3) subjects with a CVD but no experience of either an MIor a stroke. The frequency and severity of depressive symptoms did not differsignificantly in the 3 subgroups. CVD subjects with no MI or stroke hadalmost as high frequencies of depressive symptoms and vital exhaustion aspatients who experienced stroke or MI. The strength of relationships betweenthese psychological variables and CVDs do not differ significantly from therelationships between hypertension or diabetes and CVDs. Depressive symp-toms and increased vital exhaustion have exceptionally high comorbidity withCVDs. The authors detected the same high comorbidity among patients witha milder CVD and without stroke or MI. The assessment and management ofdepressive symptoms and vital exhaustion should be routine procedure in clin-ical cardiology.Index Terms: CVD, depression, stroke, vital exhaustion

Cardiovascular disorders (CVDs) are major public healthproblems worldwide. Community-based prevention ofCVDs is crucial in efforts to improve the morbidity status ofpopulations. Community-based prevention requires aknowledge of behavioral and lifestyle variables as well as

Dr Purebl, Dr Csoboth, and Ms Szumska are assistant professors,Ms Birkts is a PhD student, and Dr Kopp is a professor and direc-tor at the Institute of Behavioural Sciences, Semmelweis University,Budapest, Hungary. Copyright © 2006 Heldref Publications

the underlying psychological mechanisms. Many psycho-logical factors have been suspected as risk factors in CVDs,and there is a substantial body of research demonstratingthe contribution of psychological factors to cardiovascularmorbidity and mortality. Increasing evidence supports thepossible role of negative emotional states, distress, and atti-tudes such as hostility.1 ,2

Depressive symptoms are the most consistently docu-mented psychological factors in coronary artery disease(CAD). 3-7 Coronary patients have an approximately three-

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RISK FACTORS OF CARDIOVASCULAR DISORDER

fold higher frequency of depression than the general popu-lation.8 Depressive symptoms are predictors of negative car-diac events in the presence of CVDs,9-13 and increase therisk of future coronary heart disease among healthy indi-viduals.

3,4,'0

Some studies have suggested that, as well as clinicallysignificant major depression, mild to moderate depressivesymptoms not fulfilling the diagnostic criteria of majordepression may also carry increased risk of a cardiacevent.'4,"5 In a series of studies, Frasure-Smith, Lesp6rance,and colleagues demonstrated that patients scoring 10 ormore points on the Beck Depression Inventory (BDI), indi-cating mild to moderate subthreshold depressive symptoms,have a higher rate of further negative cardiac events (eg, non-fatal MI and cardiac death).", 6 One of their studies foundthat cardiac patients with 10 or more BDI points have almostas high a mortality rate as cardiac patients with clinicalmajor depression." However, another study demonstratedthe different nature of mild and more severe depressivesymptoms. Although an improvement in mild depressivesymptoms was associated with less cardiac mortality, highinitial depression scores were associated with worse long-term outcome regardless of symptom changes.' 6 Otherresearchers found a positive correlation between severity ofdepressive symptoms and cardiovascular risk.'1317-18

Comorbidity between depressive symptoms and MI isvery common. Some studies found major depression afterMI of 16%-23% and subthreshold ("minor") depressivesymptoms of 15%-25%.9,19 A more recent study using theBDI found 23.5% with mild subthreshold depression (BDI10-18) and only 8.8% with moderate or severe depres-sion. 16 However the majority of large-scale studies focus onMI, and there are few data on coronary artery disease(CAD) patients without histories of MI.

The investigation of depression and CVDs in an interac-tive framework is of major importance. According to theWorld Health Organization Global Burden of Disease Sur-vey, these 2 disorders are estimated as the top underlyingcauses of disability-adjusted life years,2" and there is anemerging need for understanding all aspects of the relation-ship between depression and CAD.

Exhaustion could be another cardiovascular risk factor.Cole et al found exhaustion to be associated with a twofoldincrease in the risk of CAD.2" Vital exhaustion22-23 focuses ona triad of symptoms: (1) fatigue, (2) irritability, and (3)demoralized feelings. Some studies suggest that vital exhaus-tion is separate from depression as a cardiovascular risk fac-tor.2 3

26 On the other hand, Wojciechowski et al demonstrat-ed a strong (virtually identical) correlation between vitalexhaustion and 2 different depression questionnaires and dis-

puted the separate conceptual identity of these entities.2 7 Inan earlier Hungarian study, Kopp et al also found a highlysignificant correlation and a substantial common variancebetween depression and vital exhaustion, but also foundimportant discriminating factors (level of disability, differentbehavioral factors, etc.).28 In the more recent study of Kudiel-ka et al, vital exhaustion and depressive symptoms showedsimilar common variance to the previously mentioned studyof Kopp et al, implying their interrelationship as well theirdiffering entities.29 A large-scale study of depression andvital exhaustion in a common arrangement is needed toreveal the different roles of these entities. Research onexhaustion, depressive symptoms, and cardiovascular mor-bidity is especially important in the Central Eastern Europeancountries, where there is a dramatic increase in reported car-diovascular morbidity and mortality.3 0-32

Our aim in this study was to investigate the relationshipsbetween depressive symptomatology and vital exhaustion intheir association with CVDs. Another aim was to establishwhether patients with MI or stroke display any differencesfrom those who have not experienced stroke or MI but havebeen treated for CVDs. This question was not addressed inthe earlier Hungarian survey, and the majority of interna-tional studies focus on patients who have already had an MI.

METHOD

Procedure

We constructed the sample from a national representativestratified study (Hungarostudy 2002). The survey representedthe Hungarian population by gender and age distribution(aged > 18 years) and 150 geographical subregions. The sub-jects in the stratified sample were randomly selected from thedatabase of Statistics Hungary 2001 (Ministry of InternalAffairs). A total of 12,643 participants completed a compre-hensive questionnaire battery during a home interview bytrained interviewers. The general aim of the Hungarostudywas to assess interrelationships between health, psychologicalfactors, and socioeconomic background in a representativecross-sectional sample. The general refusal rate was 17.7%,although there were differences by settlement type; largecities and urban areas had higher refusal rates, the highestbeing in the capital, Budapest (30.0%). The highest estimatedstratification error was 2.2% in men aged 18-39 years, with-in the limits of the permitted statistical deviation. 33 The Hun-garostudy researchers surveyed all settlements with a popula-tion greater than 10,000, and drew the rest of the sample fromrandomly selected smaller towns and villages. The age cohortselected for this analysis was 35 years and over (n = 11,122).The whole sample consisted of men and women aged > 18

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PUREBL ET AL

years. We selected only those aged >_ 35 years for our analy-sis. We measured the history of treatment for CVD, stroke,and Mi. We also asked about treatment for hypertension anddiabetes mellitus to compare the strength of associationbetween coronary heart disease, depression, vital exhaustion,and these 2 traditional risk factors.

Instruments

We constructed a comprehensive 700-item test battery with-in the framework of the survey. We drew the questions forthis study from the following scales and questionnaires:

Shortened Beck Depression Inventory. This 9-item Hun-garian adaptation of the BD134 showed a strong correlationwith the full 21-item version3 6.37 and proved a useful andbeneficial device for screening depressive symptoms in for-mer representative population surveys. 2834,37

Hungarian Adaptation of the Maastricht Vital ExhaustionQuestionnaire. This shortened version of the original 21-itemquestionnaire developed by Appels et a122-23 comprises those9 items that were most representative of the construct. Thisshortened version has excellent psychometric properties andwas tested in a subsequent representative survey.28

Identification of Individuals with CVD, Stroke, MI,Hypertension, and Diabetes

We asked the subjects to answer the following questionsconcerning cardiovascular and cerebrovascular morbidity:

1. Have you ever been treated because of cardiovasculardisease?

2. Have you ever been treated for stroke?3. Have you ever been treated for myocardial infarction?4. Have you ever been treated for hypertension?5. Have you ever been treated for diabetes mellitus?The participants scored the answers according to a 4-

point yes or no answer scale: I = I never have. . ., 2 = OnceI was treated for ... , 3 = I was involved with in out-patient treatment within the past year, and 4 = I was hospi-talized with within the past year.

We considered individuals as having these disorders if theyanswered yes for the second, third, or fourth answers to thesequestions, because these diseases are chronic conditions. Wedid not examine age of onset and severity. We set up 3 CVDgroups for analysis: (1) subjects with stroke, (2) subjects withMI, and (3) subjects who have CVD but neither stroke nor MI.

Statistical Analysis

We used the SPSS 8.0 statistical program package (SPSS,Inc, Chicago, IL) for analysis. To assess the interactions,we transformed continuous variables into categorical vari-ables. For the shortened version of BDI, we used the cut-

off values recommended by the literature of the Hungari-an version (10-18 = mild subthreshold depressive symp-toms, >_ 19 = clinically significant depressive symp-toms). 28',3 For vital exhaustion, we constructed 2categories with the cutoff of median (mean = 2.58, medi-an = 2.0), as in a previous community survey. 21 We con-sidered p values < .05 to be statistically significant. Weadministered the chi-square test to assess the odds ratio(OR) for CVDs associated with depressive symptoms. Weused forward conditional logistic regression analysis witha .50 classification cutoff and .05-.1 probabilities for step-wise for assessing the strength of association among car-diovascular morbidity, depression, vital exhaustion,hypertension, and diabetes with the interpretation ofExp(B) with 95% confidence intervals (CI).

RESULTS

Total Sample

In the total sample, (n = 1,749) we found a prevalence rateof 20.3% for CVDs, as shown in Table 1.

Women had a significantly higher prevalence (OR = 1.44,95% confidence interval [CI] = 1.30-1.59) of CVDs. Theprevalence of stroke was equal for both sexes (5.8%, n =501). The overall prevalence rate for Mi was 4.5% percent(n = 386). Men demonstrated significantly higher frequen-cies of MI (OR = 1.93, CI = 1.57-2.37). The frequency ofincreased vital exhaustion was 49.1% (n = 3,969) with asignificantly higher female contribution (OR = 1.76, Cl =1.63-1.90). The prevalence rate in both depression cate-gories was 17.1% (subthreshold n = 1,487, clinical n =1,489), slightly but significantly higher for women in bothcategories (subthreshold, OR = 1.26, Cl = 1.10-1.40; clini-cal, OR = 1.31, CI = 1.18-1.47).

Depression and vital exhaustion as continuous variablesshow significant moderate correlation (Pearson's r = .667)and a substantial common variance (r2 = .448). Depressionand vital exhaustion categories demonstrate moderate cor-relation ((D = .495, p = .000).

Cardiovascular Subgroup

The overall frequency of subthreshold depressive symptomswas 22.0% in the total cardiovascular subgroup, almost thesame (22.3%) among the cardiovascular patients withoutMI or stroke, 20.5% among MI patients, and 22.6% amongstroke patients. We did not find significant gender differ-ences except among stroke patients (for women, OR = 1.78,Cl = 1.10-2.93). The prevalence rates of depressive symp-toms for men and women in the different CVD subgroupsare presented in Table 2.

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The frequency of clinical depression (moderate or severedepressive symptoms) was 30.1% in the cardiovascularsubgroup as a whole, 27.4% for cardiovascular patientswith no MI or stroke, 30.9% for MI patients, and 37.6% forstroke patients. We did not detect any significant genderdifferences in either the cardiovascular group as a whole orthe 3 subgroups.

Increased vital exhaustion was frequent in the cardiovas-cular group (69.7%) and all subgroups (67.1% for the sub-group with no MI or stroke, 67.4% for MI patients, and74.6% for stroke patients). We found significant gender dif-ferences in the cardiovascular group as a whole (OR = 1.41,CI = 1.13-1.76) and among patients with no consequences(OR = 1.55, CI = 1.22-1.97), appeared in the MI subgroupas a tendency (OR = 1.59, CI = .99-2.56, D = .051) andwere insignificant in the stroke subgroup.

Interrelationship Among Psychological Risk Factors,Hypertension, and Diabetes

We examined the impact of depression and vital exhaus-tion on cardiovascular morbidity by logistic regressionanalysis and compared them with the impact of the well-documented traditional risk factors of hypertension anddiabetes. The relationships among psychosocial variables,cardiovascular subgroups, hypertension, and diabetes arepresented in Figure 1.

The nonstroke, non-MI cardiovascular subgroup showeda significant relationship to all variables included in theanalysis. Hypertension, exp(B) = 1.82, CI = 1.60-2.07, andvital exhaustion, exp(B) = 1.75, CI = 1.52-2.03, demon-strated the strongest associations and diabetes the weakest,exp(B) = 1.27, CI = 1.04-1.54, but there were no significantdifferences in strength of association.

Behavioral Medicine

TABLE 1. Gender-Related Prevalence Rates for Cardiovascular Disorders,Depression, and Vital Exhaustion

Women Men

Characteristic n % n %

Cardiovascular disease total 1,093 22.4 654 17.5Myocardial infarction 151 3.1 235 6.3Stroke 285 5.8 216 5.8Subthreshold depressive symptoms 885 18.0 602 15.9Clinical depression 905 18.4 581 15.3Vital exhaustion 2,512 55.0 1,452 41.4

TABLE 2. Prevalence of Depressive Symptoms and Vital Exhaustion in Cardiovascular Disorders (CVDs)

Women Men

Subthreshold Clinical Vital Subthreshold Clinical Vitaldepression depression exhaustion depression depression exhaustion

CVDs n % n % n % n % n % n %

Total 241 22.7 327 30.8 716 72.5 133 20.9 183 28.8 388 65.1CVDs with no

consequences 206 22.9 253 28.1 589 70.6 104 21.2 127 25.9 281 60.8MI 25 17.4 48 33.3 100 73.5 52 22.4 68 29.3 132 63.5Stroke 69 25.6 106 39.3 190 76.3 38 18.6 72 35.3 137 72.5

Note. Total = all persons with cardiovascular disorders; CVDs with no consequences = persons with cardiovascular disorders but not stroke ormyocardial infarction; MI = persons with myocardial infarction.

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PUREBL ET AL

We found similar results in the subgroup of patients whohad experienced MI. All variables demonstrated significantassociation with the subgroup except subthreshold depres-sion, exp(B) = 1.23, CI = .90-1.67. We found the weakestrelationship with vital exhaustion, exp(B) = 1.51, CI =1.15-1.98, and the strongest with hypertension, exp(B) =1.84, CI = 1.46-2.31, but the differences in the strength ofassociations were not significant.

The picture was little different in the stroke subgroup. Inour study diabetes did not display significant associationwith stroke. The strongest relationship was with hyperten-sion, exp(B) = 3.16, OR = 2.57-3.89, and was significantlystronger than those with vital exhaustion and subthresholddepression, but not significantly stronger than that with clin-ical depression, exp(B) = 2.2, CI = 1.71-2.86. The strengthof associations among depression categories and vitalexhaustion did not differ significantly.

COMMENT

The exceptionally high prevalence rates of CVD-approx-imately one fifth of the Hungarian population over the ageof 35 have been treated for CVDs-are similar to theresults of previous Hungarian studies28 ,37 and other datafrom Central Eastern Europe. 3° Approximately half of thepopulation with cardiovascular problems exhibit depressivesymptoms. In the cardiovascular subgroup without MI or

stroke, the proportion of mild subthreshold and clinicaldepressive states are approximately equal, and in the MIsubgroup the overall frequency of depressive symptomswas similar, with a slightly higher proportion of clinicallydepressive cases. In the stroke subgroup, women have ahigher frequency of overall depressive symptoms (64.9%),made up mostly of clinical depression (39.3%). The over-all frequency of depressive symptoms among men in thissubgroup is 53.9%, made up mostly of clinical depression(35.3%).

Gender differences emerged for both depression cate-gories in the total sample, but not significantly among car-diovascular patients except for mild subthreshold depres-sive symptoms in the stroke subgroup.

Our findings indicate exceptionally high comorbiditybetween depressive symptoms and cardiovascular disor-ders. It is surprising that the comorbidity among cardiovas-cular cases with no MI or stroke was as high as in the sub-groups with MI or stroke. This may suggest that there arefactors other than disease severity and negative conse-quences affecting the strength of the relationship betweendepressive symptomatology and CVDs. Other complexconnections involving the psychophysiological mechanismsof stress response and depressive symptomatology couldproduce circular interactions with cardiovascular patho-physiology. Further research is needed to clarify the nature

[]CVD with no consequences * Stroke EMyocardial infarction

0

3.50.e•3.00-I

. 2.5o-

S1.50-

S1.OO.

0.50Subtreshold Clinical Vital Hypdepression depression exhaustion

Psychological Variable

FIGURE 1. Relationships among psychological variables. CVD = Cardiovascular disease.

Vol 31, Winter 2006

ertension

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RISK FACTORS OF CARDIOVASCULAR DISORDER

and the functional elements of these interactions and theirimpact on the course of CVDs and depression.

The majority of cardiovascular patients suffer from vitalexhaustion (76.1%-74.6% in the different subgroups). Gen-der differences are significant but decrease with severity:they show up clearly in the non-MI-nonstroke subgroup,but are only a tendency in the MI group, and are not signif-icant at all in the stoke subgroup.

Depression and vital exhaustion showed moderate corre-lation. We found the gender differences significantly higherin the total sample than in the depression categories. Theinvestigation of depression categories and vital exhaustionin the same multivariate arrangement revealed that bothdepression and vital exhaustion have significant indepen-dent associations with cardiovascular morbidity. Althoughthese results lend support to the concept of vital exhaustionas an independent factor, they still show that it has a sub-stantial common variance with depression. Further investi-gations are needed to reveal the nature of the relationshipbetween vital exhaustion and depressive symptoms.

In all the cardiovascular subgroups, cardiovascular mor-bidity appeared to have a similarly strong association withthe psychological variables as with hypertension and dia-betes. The associations were of similar strength through-out, except for hypertension in the stroke subgroup. Thepsychological characteristics are thus equally associatedwith cardiovascular morbidity as the 2 traditionally exam-ined risk factors.

Limitations

Our survey has some important limitations. First, cross-sec-tional sampling could not reveal the directions of the inter-actions and imposed severe limitations concerning causality.Second, disease categories are based on self-reports, and noinformation was available about the onset and severity ofdisease.

Our data clearly demonstrate that depressive symptomsand vital exhaustion are very common problems amongcardiovascular patients. In view of the high prevalence ofCVDs and the increasing importance of both depressionand cardiovascular problems projected for the nearfuture,2 0 we suggest that the screening and treatment ofdepression could be equally important in clinical cardiol-ogy as the management of hypertension, lipid and choles-terol abnormalities, and behavioral factors, such as dietand exercise.

ACKNOWLEDGMENTSThe national representative study reported in this article is sup-

ported by the United Nations Development Program (UNDP) pro-

ject No. HUN/00/002/A/01/99, the National Research Fund(OTKA) projects OTKA TS-40889(2002), and TS 049785(2004)Scientific School Grants NKFP 1/002/2001 and NKFP16/020/2004.

NOTE

For comment or further information, please address correspon-dence to Gy6rgy Purebl, MD, Institute of Behavioural Sciences,Semmelweis University, Nagyvdrad t6r 4, H- 1089 Budapest, Hun-gary (e-mail: purgyor@net.sote.hu).

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TITLE: The Relationship of Biological and Psychological RiskFactors of Cardiovascular Disorders in a Large-scaleNational Representative Community Survey

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