Abstract

Aims Mental depression is associated with an increased risk of cardiovascular mortality, but the reasons for this association are not well known. We tested the hypothesis that depressive symptoms (DS) may specifically increase the risk of sudden cardiac death (SCD) among the elderly subjects.

Methods All persons aged 70 years or over of a defined area in Northern Finland (n=1113) were the target population, and 915 (82%); 336 men and 579 women, participated in the questionnaire on depressive symptoms according to the Short Zung Depression Rating Scale. Potential risk factors of SCD were examined in the same connection, and the mode of death was examined via the official death certificates during the following eight years. SCD and non-SCD as well as overall mortality, cardiac mortality and non-fatal myocardial infarction (MI) were the end-points.

Results Four hundred and seventy-six subjects out of 915 (52%) died during the follow-up of 8 years. Thirty-eight of deaths were SCDs (8%) and non-SCD occurred in 106 subjects (22%). In univariate analysis, a high score of DS was a significant predictor of subsequent SCD; hazard ratio 2.67 (95% confidence interval 1.34–5.32), non-SCD; 1.67 (1.06–2.63), cardiac mortality; 1.90 (1.30–2.78) and total mortality; 1.88 (1.52–2.32), but not that of non-fatal MI; 1.74 (0.89–3.38). SCD was also predicted by gender (P<0.01), MI (P<0.01) and tablet- or insulin-treated diabetes mellitus (P<0.01). In multivariate Cox regression analysis by adjusting for the clinical variables, high score of DS remained as a significant predictor of SCD; hazard ratio 2.74 (1.37–5.50) and total mortality; 1.70 (1.37–2.10), but not of cardiac mortality 1.50 (0.998–2.27), non-SCD; 1.38 (0.85–2.24) and non-fatal MI; 1.37 (0.69–2.71).

Conclusion Depressive symptoms increase the risk of SCD, but not that of non-SCD and non-fatal MI among the elderly subjects.

Introduction

A high proportion of deaths due to coronary artery disease are sudden deaths, which by definition are unexpected deaths within 1h after the onset of symptoms.1Despite this well established problem in clinical cardiology and public health, there is relatively little information on the risk factors and strategies for prevention of sudden cardiac death (SCD) in general population.Previous epidemiological surveys have shown that several demographic and clinical variables, such as male gender, history of congestive heart failure (CHF), prior myocardial infarction (MI), hypertension,2,3altered heart rate variability,4ambient ventricular arrhythmias, and some general cardiovascular risk factors2increase the risk of SCD in general population. The incidence of SCD also increases with advancing age. The predictive value of each of these risk variables has been relatively low, however.1,5

Numerous previous data have shown that depressive symptoms increase all-cause mortality, as well as cardiovascular morbidity and mortality.6–19Irvine et al.20found among the patients with a prior MI, that depression predicted the occurrence of SCD after controlling for other risk factors. Self-reported symptoms of fatigue appeared to explain even more specifically this association.

Until now, the reasons for the associations between depression and CV mortality are not well established in general population. It is not known whether DS itself enhance the progression of CHD or whether DS increase the risk of specific mode of cardiovascular death, such as SCD. To test this hypothesis, we conducted a population-based study in order to examine the risk of SCD in regard to depressive symptoms (DS) in a random sample of elderly subjects.

Methods

The institutional ethics committee approved the study protocol, and informed consent was obtained before interviewing the subjects.

Depressive symptoms

The population consisted of all persons aged 70 years or over of a defined area in Northern Finland on September 1, 1991 (n=1113), of whom 915 (82%); 336 men and 579 women, participated in the questionnaire on depressive symptoms according to the Short Zung Depression Rating Scale (SZDRS). The scale is composed of ten questions scored 1–4 (seldom or never, some of the time, good part of the time, most of the time), for all of which the participants were requested to select an appropriate response. The individual questions are: I feel down-hearted and blue (1–4), I have trouble sleeping at night (1–4), morning is when I feel the best (4–1), I can eat as much as I used to (4–1), I get tired for no reason (1–4), I find it difficult to make decisions (1–4), I feel hopeful about the future (4–1), I feel that I am useful and needed (4–1), my life is somewhat empty (1–4), I still enjoy things I used to do (4–1). The nurse interviewer reviewed the responses, and assisted the participant to fill in the questionnaire, if needed. Existing depressive symptoms were defined as SZDRS-score of >̄28 on the direct scale 10–40.21

Other clinical data

Occurrence of chest pain (no, once or twice a week, every other day, daily), diabetes mellitus (no, diet-, tablet-, or insulin-treated), any current smoking and frequency of use of alcohol (no, fewer than once in a month, about once or twice in a month, at least once in a week, daily), were recorded by means of standardized questionnaires. Presence of diagnosis of hypertension and congestive heart failure (CHF) were noted by the examining physician from the medical records of the health centres. National health insurance documents were also reviewed to record hypertension and CHF requiring medication. The examining physician recorded current medication use by interviewing the participants. Additional information was derived from interviews, prescriptions and drug packages that the subjects had been asked to bring to the examination. Weight and height in light clothing without shoes were measured and body mass index (BMI) (kg/m2) was calculated by one of the nurses. Blood pressure (BP) (2mmHg accuracy) was measured after 5min rest with the subject in supine position, using a mercury manometer.22

Sudden cardiac deaths

Death certificates from the Central Statistical Office of Finland were used to record deaths due to codes 391–414, 420-429 (ICD-9), I05-I25, I30-I52 (ICD-10) in the cohort from the day of measuring DS up to the end of the follow-up period, 31 December 1999. Cardiac deaths were defined as sudden and non-sudden. After careful examination of all the death certificates, the SCDs were defined as deaths that occurred within one hour from the onset of symptoms. If the person had experienced worsening chest pain, or if he/she was found dead without a recently witnessed health status, it was not defined as a SCD.

Non-fatal myocardial infarctions (MI)

Data on non-fatal cases of MI were derived from the statistics of the Oulu University Hospital and were based on codes 410 00–410 99 (ICD-8) during 1976–1986 and codes 4100–4109 (ICD-9) during 1987–1995 and I21-I23 (ICD-10) from that time onwards up to the end of follow-up period, 31 December 1999.

Statistical analyses

Cross-tabulations were used to assess the associates of DS, and continuous variables were compared by using the Student t test.

Person time expressed as persons years (PY) for the incidence rates were calculated until move to other districts, death or until the end of follow-up period. Kaplan–Meier survival curves were used to present survival distributions and the test was based on Cox–Mantel procedure, comparing persons with SZDRS-score of >̄28 to those with score of <28 points.

Univariable and multivariable Cox regression analyses were used to analyze survival time until SCD, non-SCD, cardiac death, death, and first non-fatal MI. The results are summarized as hazard ratios (HRs) with 95% confidence intervals (95% CIs). HRs as regards DS were calculated against a SZDRS-score of >̄28. DS was also considered as a continuous variable, calculating HR against one point increase on the SZDRS 10–40. Age, sex, systolic BP (SBP), hypertension, chest pain, history of MI, CHF, diabetes mellitus, current smoking and alcohol consumption habits, BMI, use of calcium antagonist and beta blocker medication were first tested by univariate Cox regression for dependence on each of the end-points. In these analyses, age, SBP, and BMI were considered as continuous variables. Depending on statistical significance (95% confidence interval not crossing 1 or P<0.05), variables were selected as covariates in multivariable Cox proportional hazards analyses. The proportional hazards assumptions were tested by constructing interaction terms between the variables and time to each end-point.23Cox regression analyses showed no statistically significant interactions with time (each P>0.05). We also tested possible interactions between DS and the covariates which increased risk of any of the end points. No statistically significant interactions were found (each P>0.05), when interaction terms, along with the individual variables, were entered in Cox regression analyses.

The model selection is based on the stepwise principle, where the limit to enter and to remove a variable were 0.10 and 0.15, respectively. These are the default limits of the software applied. Commercially available software (BMDP StatisticalSoftware Inc, Los Angeles, California) on a SUN/UNIX mainframe computer (Sun Microsystems, Inc, Palo Alto, California) was used to carry out the computation.

Results

Baseline characteristics

The characteristics of the population according to presence and absence of DS are presented in Table 1. Persons with DS were older, experienced more often chest pain, tablet- or insulin treated diabetes mellitus, hypertension, CHF, and had lower BMI and SBP than the persons without DS.

Table 1

Characteristics of the study population according to presence of depressive symptoms (DS)


Characteristic
 

Total (n=915)
 

DSapresent (n=175)
 

DSa absent (n=740)
 

P value
 
Age, years 78±5 79±6 76±5 0.001 
Systolic blood pressure, mmHg 156±25 151±27 157±25 0.001 
Body mass index, kg/m2 28±5 27±5 28±5 0.048 
Male sex 336 (37) 52 (30) 284 (38) 0.032 
Hypertension 298 (35) 65 (42) 233 (33) 0.042 
Chest pain at least once in a week 339 (37) 95 (54) 244 (33) 0.001 
History of myocardial infarction 67 (7) 16 (9) 51 (7) 0.304 
Congestive heart failure 326 (36) 79 (45) 247 (33) 0.003 
Diabetes mellitus 191 (21) 43 (25) 148 (20) 0.181 
Tablet- or insulin-treated diabetes mellitus 106 (12) 26 (15) 80 (11) 0.026 
Any current smoking 67 (7) 13 (7) 54 (7) 0.952 
Use of alcohol at least once in a month
 
153 (17)
 
18 (10)
 
135 (18)
 
0.011
 

Characteristic
 

Total (n=915)
 

DSapresent (n=175)
 

DSa absent (n=740)
 

P value
 
Age, years 78±5 79±6 76±5 0.001 
Systolic blood pressure, mmHg 156±25 151±27 157±25 0.001 
Body mass index, kg/m2 28±5 27±5 28±5 0.048 
Male sex 336 (37) 52 (30) 284 (38) 0.032 
Hypertension 298 (35) 65 (42) 233 (33) 0.042 
Chest pain at least once in a week 339 (37) 95 (54) 244 (33) 0.001 
History of myocardial infarction 67 (7) 16 (9) 51 (7) 0.304 
Congestive heart failure 326 (36) 79 (45) 247 (33) 0.003 
Diabetes mellitus 191 (21) 43 (25) 148 (20) 0.181 
Tablet- or insulin-treated diabetes mellitus 106 (12) 26 (15) 80 (11) 0.026 
Any current smoking 67 (7) 13 (7) 54 (7) 0.952 
Use of alcohol at least once in a month
 
153 (17)
 
18 (10)
 
135 (18)
 
0.011
 
a

DS=Short Zung Self-Rating Depression scale >̄⩾28; Numbers are n (%) or mean±SD, and they may differ because of missing data; p value is from Chi-Square test (dichotomised) or Student t-test (continuous) variables.

Incidence of SCD and non-SCD

There were 38 (7/1000PY) SCDs, of which 11 were confirmed by autopsy, 106 (19/1000PY) non-SCDs, and 332 non-cardiovascular (CV) deaths in the cohort during the follow-up period of 8 years. Twenty-two (11/1000PY) SCDs occurred in men, and 16 (4/1000PY) in women. Non-SCDs occurred in 35 (18/1000PY) men and 71 (19/1000PY) women.

Survival analyses

Kaplan–Meier survival curves on the probability of remaining free of SCD as regards DS are presented in Fig. 1. According to univariable Cox regression analyses, DS, male sex, history of MI, and tablet- or insulin-treated diabetes mellitus were associated with subsequent SCD. Multivariable Cox regression analysis, with all these variables entered in the model, showed that male sex, history of MI, tablet- or insulin-treated diabetes mellitus, and DS were predictors of subsequent SCD (Table 2). Considered as a continuous variable in univariable and multivariable analysis, DS was associated with subsequent SCD; HR (95% CI) 1.09 (1.03–1.16) and 1.09 (1.02–1.16), respectively.

Fig. 1

Kaplan–Meier plots on the probability of remaining free of sudden cardiac death in depressive and non-depressive older adults

Fig. 1

Kaplan–Meier plots on the probability of remaining free of sudden cardiac death in depressive and non-depressive older adults

Table 2

Risk factors of sudden cardiac death according to Cox regression analyses


Variable
 

(Units)
 

Univariable hazard ratioa(95%CI)
 

Multivariable hazard ratioa(95%CI)
 
Age (+1 year) 1.04(0.98–1.11)  
Systolic blood pressure (+2mmHg) 1.00(0.99–1.01)  
Body mass index (+1kg/m20.93(0.87–1.01)  
Male sex (0,1=yes) 2.57(1.35–4.89) 2.79(1.46–5.34) 
Hypertension (0,1=yes) 0.70(0.34–1.45)  
Chest pain at least once in a week (0,1=yes) 1.81(0.96–3.42)  
History of myocardial infarction (0,1=yes) 3.24(1.43–7.37) 2.46(1.07–5.69) 
Congestive heart failure (0,1=yes) 1.58(0.83–3.00)  
Diabetes mellitus (0,1=yes) 1.37(0.65–2.90)  
Tablet- or insulin-treated diabetes mellitus (0,1=yes) 2.35(1.03–5.37) 2.42(1.05–5.57) 
Any current smoking (0,1=yes) 1.67(0.59–4.70)  
Use of alcohol at least once in a month (0,1=yes) 1.49(0.71–3.16)  
Depressive symptomsb (0,1=yes) 2.67(1.34–5.32) 2.74(1.37–5.50) 
Use of calcium antagonist (0,1=yes) 1.82(0.88–3.78)  
Use of beta blocker
 
(0,1=yes)
 
0.95(0.39–2.28)
 

 

Variable
 

(Units)
 

Univariable hazard ratioa(95%CI)
 

Multivariable hazard ratioa(95%CI)
 
Age (+1 year) 1.04(0.98–1.11)  
Systolic blood pressure (+2mmHg) 1.00(0.99–1.01)  
Body mass index (+1kg/m20.93(0.87–1.01)  
Male sex (0,1=yes) 2.57(1.35–4.89) 2.79(1.46–5.34) 
Hypertension (0,1=yes) 0.70(0.34–1.45)  
Chest pain at least once in a week (0,1=yes) 1.81(0.96–3.42)  
History of myocardial infarction (0,1=yes) 3.24(1.43–7.37) 2.46(1.07–5.69) 
Congestive heart failure (0,1=yes) 1.58(0.83–3.00)  
Diabetes mellitus (0,1=yes) 1.37(0.65–2.90)  
Tablet- or insulin-treated diabetes mellitus (0,1=yes) 2.35(1.03–5.37) 2.42(1.05–5.57) 
Any current smoking (0,1=yes) 1.67(0.59–4.70)  
Use of alcohol at least once in a month (0,1=yes) 1.49(0.71–3.16)  
Depressive symptomsb (0,1=yes) 2.67(1.34–5.32) 2.74(1.37–5.50) 
Use of calcium antagonist (0,1=yes) 1.82(0.88–3.78)  
Use of beta blocker
 
(0,1=yes)
 
0.95(0.39–2.28)
 

 
a

Hazard ratio is for the unit expressed in parentheses.

b

Short Zung Depression Rating Scale (10-40) >̄⩾28; Variables entered in the multivariable analysis: male sex, history of MI, tablet- or insulin-treated diabetes mellitus, depressive symptoms

Removal of users of anti-depressants did not change the main results, that DS was associated with subsequent SCD; univariable HR (95% CI) 2.17 (1.02–4.65). Correspondingly, removal of persons with prior MI did not change the result; 2.90 (1.36–6.18).

The individual four-scored items of the SZDRS were tested, one at a time, for their dependence with subsequent SCD by using univariable Cox regressions. Each item was dichotomized, and scores three and four were compared with scores one and two. The following items were associated (P<0.05) with subsequent SCD: I feel down-hearted and blue, I can eat as much as I used to, and I still enjoy things I used to. Fatigue for no reason was not (P>0.05) associated with subsequent SCD.

In univariable Cox regression analyses, higher age, DS, diabetes mellitus, tablet-or insulin treated diabetes mellitus, CHF, history of MI and chest pain were associated with subsequent non-SCD. In a multivariable analysis, DS was no more a significant predictor of non-SCD, but higher age, tablet- or insulin treated diabetes mellitus, and history of MI were significantly associated with subsequent non-SCD (Table 3). Considered as a continuous variable in univariable and multivariable analysis, DS was not associated with subsequent non-SCD; HR (95% CI) 1.03 (0.998–1.07) and 1.01 (0.97–1.05), respectively.

Table 3

Risk factors of non-sudden cardiac death according to Cox regression analyses


Variable
 

(Units)
 

Univariable hazard ratioa(95%CI)
 

Multivariable hazard ratioa(95%CI)
 
Age (+1 year) 1.09(1.05–1.13) 1.11(1.07–1.15) 
Systolic blood pressure (+2mmHg) 1.00(0.99–1.00)  
Body mass index (+1mmHg) 0.99(0.95–1.03)  
Male sex (0,1=yes) 0.93(0.62–1.40)  
Hypertension (0,1=yes) 1.03(0.69–1.56)  
Chest pain at least once in a week (0,1=yes) 1.57(1.09–2.34) 1.15(0.75–1.73) 
History of myocardial infarction (0,1=yes) 2.96(1.78–4.91) 2.63(1.50–4.62) 
Congestive heart failure (0,1=yes) 2.03(1.39–2.98) 1.41(0.94–2.11) 
Diabetes mellitus (0,1=yes) 2.48(1.67–3.69)  
Tablet- or insulin-treated diabetes mellitus (0,1=yes) 3.88(2.51–5.99) 3.35(2.10–5.35) 
Any current smoking (0,1=yes) 1.68(0.90–3.13)  
Use of alcohol at least once in a month (0,1=yes) 1.07(0.65–1.75)  
Depressive symptomsb (0,1=yes) 1.67(1.06–2.63) 1.38(0.85–2.24) 
Use of calcium antagonist (0,1=yes) 1.85(1.19–2.86) 1.32(0.82–2.10) 
Use of beta blocker
 
(0,1=yes)
 
1.12(0.68–1.85)
 
 

Variable
 

(Units)
 

Univariable hazard ratioa(95%CI)
 

Multivariable hazard ratioa(95%CI)
 
Age (+1 year) 1.09(1.05–1.13) 1.11(1.07–1.15) 
Systolic blood pressure (+2mmHg) 1.00(0.99–1.00)  
Body mass index (+1mmHg) 0.99(0.95–1.03)  
Male sex (0,1=yes) 0.93(0.62–1.40)  
Hypertension (0,1=yes) 1.03(0.69–1.56)  
Chest pain at least once in a week (0,1=yes) 1.57(1.09–2.34) 1.15(0.75–1.73) 
History of myocardial infarction (0,1=yes) 2.96(1.78–4.91) 2.63(1.50–4.62) 
Congestive heart failure (0,1=yes) 2.03(1.39–2.98) 1.41(0.94–2.11) 
Diabetes mellitus (0,1=yes) 2.48(1.67–3.69)  
Tablet- or insulin-treated diabetes mellitus (0,1=yes) 3.88(2.51–5.99) 3.35(2.10–5.35) 
Any current smoking (0,1=yes) 1.68(0.90–3.13)  
Use of alcohol at least once in a month (0,1=yes) 1.07(0.65–1.75)  
Depressive symptomsb (0,1=yes) 1.67(1.06–2.63) 1.38(0.85–2.24) 
Use of calcium antagonist (0,1=yes) 1.85(1.19–2.86) 1.32(0.82–2.10) 
Use of beta blocker
 
(0,1=yes)
 
1.12(0.68–1.85)
 
 
a

Hazard ratio is for the unit expressed in parentheses.

b

Short Zung Depression Rating Scale (10-40) >̄ ⩾28; Variables entered in the multivariable analysis: age, chest pain at least once a week history of myocardial infarction, congestive heart failure, tablet- or insulin-treated diabetes mellitus, depressive symptoms, use of calcium antagonist

According to a univariable Cox regression, DS was associated with all-cause mortality; HR 1.88 (1.52–2.32). In multivariable analysis, adjusted for the other statistically significant associates (P<0.05) of all-cause mortality; male sex, higher age, tablet- or insulin-treated diabetes mellitus, CHF, current smoking, and lower BMI, DS retained statistical significance; 1.70 (1.37–2.10). Considered as a continuous variable, DS was associated with all-cause mortality; univariable andmultivariable HR (95% CI) 1.06 (1.04–1.07) and 1.04 (1.02–1.05), respectively.

The univariable relative risk of cardiac mortality as regards DS was 1.90 (1.30–2.78). In multivariable analysis, after an adjustment for the statistically significant covariates (P<0.05); higher age, history of MI, use of calcium antagonist, chest pain, CHF, tablet- or insulin treated diabetes mellitus, and lower BMI, DS was not associated with subsequent cardiac death; 1.50 (0.998–2.27). As a continuous variable, DS was associated with cardiac mortality in univariable analysis; 1.05 (1.02–1.08), but not in multivariable analysis; 1.02 (0.99–1.06).

After exclusion of the persons who suffered cardiac death, we explored the risk of subsequent non-fatal MI (n=54) in regard to DS. DS was not associated with subsequent MI; univariable HR (95% CI) 1.74 (0.89–3.38). In multivariable analysis, after an adjustment for the associates of non-fatal MI; history of MI, CHF and tablet- or insulin treated diabetes mellitus (P<0.05), the corresponding relative risk was 1.37 (0.69–2.71). Considered as a continuos variable, DS was associated with subsequent non-fatal MI in a univariable analysis; 1.05 (1.00–1.11), but not in a multivariable analysis; 1.03 (0.98–1.08).

Discussion

The present results show that depression is associated with an increased risk of cardiac mortality among the elderly subjects. Depression increased specifically the incidence of SCD but not so evidently the non-SCD and non-fatal MI. Depression also remained as an independent predictor of subsequent SCD after adjustments with many known risk variables of cardiac mortality. The analyses made among the individual items of SZDRS did not support the assumption that self-reported fatigue explains this prediction.20

Several recent studies have shown that emotions, including depression, anxiety and hostility may influence the outcomes in patients with established coronary artery disease.[7–9,11,14,18–20,24]The results have been most consistent for depression.[7–9,11,14,18–20]Studies among the patients with a recent myocardial infarction have documented that depression is a strong risk factor of mortality.18,19The risk of death among the depressed post-infarction patients has been similar to that of the patients with left ventricular dysfunction or a history of previous myocardial infarction.18,19Similar associations between depression and cardiac events have also been observed among the patients with stable or unstable angina pectoris.7,8

To our knowledge, there have been no previous observational studies assessing the possible association between depression and cardiac events in random elderly populations. Post-hoc analyses of some large data sets have suggested that depression increases the risk of coronary artery disease in initially healthy individuals. The population in the present study is representative of a northern-Finnish elderly population with a relatively high participation rate and with a long follow-up. Those who did not participate (n=198), did not differ from the participants as regards gender [(males 39% vs 37%); Chi-Square 0.50, P=0.481)], and they were only 0.9 (95% CI 0.13–1.81) years older than the participants. Total mortality among the non-participants (58%) did not differ from that of the participants (52%) (Chi-Square 2.02, P=0.1557). Therefore, the results can well be generalized to elderly subjects, but further studies will be needed to document whether similar associations exist in general population of middle-aged subjects.

The previous studies assessing the impact of depression on outcomes have used total mortality, cardiac mortality, and/or combination of non-fatal and fatal cardiac events as end-points of the studies. As also previously noted,25depression seemed to predict fatal cardiac events but not non-fatal MIs. More specifically, the present results showed that depression increased the risk of SCD but not that of non-SCD. Strict criteria were used here to define the mode of death, e.g. the autopsy rate was higher than that reported in most previous studies, aimed at avoiding the potential biases in the definition of SCD.26In the present study area, there is only little disagreement between the antemortem and autopsy CHD diagnoses,27which tends to minimize the misclassification potential related to coronary deaths. Only one death due to MI occurred outside the Oulu University Hospital district. This suggests that also practically all non-fatal MIs were found, although they were recorded only in the Oulu district. Moreover, the age- and sex- specific incidence rates of SCD presented here are similar to those found in a larger population sample, in which the mode of death was reliably defined.2Therefore, the results suggest that depression is more strongly associated with the onset of fatal arrhythmia events than with other modes of cardiac events.

The risk of SCD rises dramatically as the number of CHD risk factors increases. Several known risk factors, such as previous myocardial infarction and diabetes, were also here strong predictors of SCD. However, depression emerged as an equally strong predictor of SCD as the common risk variables, and it retained its independent predictive power in multivariable analyses.

Altered cardiovascular autonomic regulation is one of the potential mechanisms explaining the association between depression and SCD. Both increased sympathetic activity and decreased parasympathetic activity enhance the vulnerability to fatal arrhythmia events.28–31Many previous studies have observed abnormalities in cardiac autonomic regulation among the depressive subjects. For example, depressive subjects have impaired heart rate variability, which has shown to be a strong predictor of sudden cardiacdeath and arrhythmia events in various populations.32,33Abnormal heart rate behaviour, reflecting altered cardiac autonomic regulation, has also been shown to predict the occurrence of SCD in a random elderlypopulation.4

Our data did not include clinical depression diagnosis. The SZDRS is validated only for screening purposes of depression in the elderly,21and identifies depressed mood, but not the severity of depression.34Therefore, we are not able to make statements about the possible association between the severity of depression and cardiac events among the elderly. We did not either estimate the significance of worsening of depression over time, which also may have prognostic importance.16

In conclusion, our results suggest that depressive symptoms increase the risk of SCD in older adults. Further studies are needed to examine the contribution of clinical depression of different severity on this risk. In particular, studies with larger population samples including different age groups and genders will be needed to examine the risk of SCD associated with depression.

1

Deceased on May 13, 2003

This study was supported in part by the Medical Council of the Academy of Finland, Helsinki, and the Foundation for Cardiovascular Research, Helsinki, Finland (HH), and in part by the Department of Health and Security of Finland. The authors wish to acknowledge Keijo Koski, MD, Chief Physician, for his contribution during the early phases of the original population study.

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