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Childhood adversities as predictors of incident coronary heart disease and cerebrovascular disease
  1. Jyrki Korkeila1,2,
  2. Jussi Vahtera3,4,5,
  3. Katariina Korkeila6,
  4. Mika Kivimäki7,
  5. Markku Sumanen8,
  6. Karoliina Koskenvuo9,
  7. Markku Koskenvuo10
  1. 1Department of Psychiatry, University of Turku, Finland
  2. 2Harjavalta Hospital, Satakunta Hospital District, Finland
  3. 3Department of Public Health, University of Turku, Finland
  4. 4Finnish Institute of Occupational Health, Helsinki, Finland
  5. 5Turku University Central Hospital, Finland
  6. 6Turku Municipal Health Care, Turku, Finland
  7. 7Department of Epidemiology and Public Health, University College London, UK
  8. 8University of Tampere, Medical School, Tampere, Finland
  9. 9Social Insurance Institution, Helsinki, Finland
  10. 10Department of Public Health, University of Helsinki, Helsinki, Finland
  1. Correspondence to Jyrki Korkeila, Department of Psychiatry, University of Turku, Kunnallissairaalantie 20, 20700 Turku, Finland; jyrki.korkeila{at}utu.fi

Abstract

Background Studies suggest that childhood adversities are important determinants of various types of later illnesses as well as poor health behaviour. However, few large-scale prospective studies have examined the associations between childhood adversities and cardiovascular disease.

Objective To investigate whether childhood adversities are associated with increased risk of incident cardiovascular disease

Design and setting Participants were 23 916 men and women in four age groups (20–24, 30–34, 40–44, and 50–54 years) from the Health and Social Support study, a longitudinal study on a random sample representative of the Finnish population. Data from national health registers on coronary heart disease and cerebrovascular disease during a mean follow-up of 6.9 years were linked to survey responses on childhood adversities. Cox proportional hazard models were adjusted for age group and potential mediators (education, health risk behaviours, diabetes and depression).

Results There was a significant linear trend between the number of childhood adversities and disease end points in women. The risk of incident cardiovascular disease was threefold among women exposed concurrently to three types of childhood adversities (financial difficulties, interpersonal conflicts and longstanding illness of a family member). Among men, increased risk was observed only among those with longstanding illness of a family member (HR=1.44; 95% CI 1.06 to 1.96).

Conclusions In this prospective population-based sample, childhood adversities were associated with a significantly increased risk of objectively verified cardiovascular disease, especially among women but to a lesser extent among men. More studies with prospective settings are needed to confirm the association and possible mechanisms.

  • Risk factors
  • epidemiology
  • cardiovascular diseases
  • psychosocial
  • psychology/psychiatry
  • coronary artery disease

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It is increasingly recognised that childhood adversities may be important determinants of various types of adult morbidity as well as poor health behaviour.1–11 Most of the studies in this field of research have focused on exposures such as childhood sexual or physical abuse, or severe neglect. Several,2–5 12 13 but not all7 studies have found support for a dose–response relationship: the greater the number and severity of childhood adversities, the more unfavourable the health outcomes. Childhood abuse has been associated with increased physical health problems but a subject's psychiatric illness substantially decreased the strength of this association.7

Socioeconomic adversity in childhood is suggested to be an important determinant of later cardiovascular disease,14 but less is known about the influence of other types of childhood adversities. Cross-sectional evidence of association between childhood adversities and self-reported cardiovascular disease has been found in some studies,15–17 but prospective studies on the associations between childhood adversities and cardiovascular disease are scarce. In this study, we aimed to investigate whether self-reported childhood adversities measured at adulthood are associated with increased risk of verified coronary heart disease (CHD) or cerebrovascular disease (CVD) in a nationally representative, prospective population sample.

Methods

Population

Data were collected from the Health and Social Support (HeSSup) study, a longitudinal study on a population sample representative of the Finnish population in the following four age groups: 20–24, 30–34, 40–44 and 50–54 years at baseline in 1998. The initial response rate of the postal survey was 40%. According to the non-response analysis,18 no significant selective health-related factors could be identified. Of the 25 901 respondents, 93% gave their written consent for health register linkages. We excluded those with register-based CHD, CVD or diabetes at baseline or with missing information on childhood adversities (n=743). In addition, 234 respondents had moved abroad and could not be followed up.

Data from national health registers on CHD and CVD during an 8-year follow-up were linked to survey responses of 23 916 (men 41%, women 59%) participants, the final cohort of this study. The Turku University Central Hospital Ethics Committee approved the study.

Measures

Childhood adversities

The occurrence of childhood adversities was assessed at baseline with a six-item survey scale with questions on long-term financial difficulties, divorce or separation of the parents, serious conflicts in the family, severe illness of a family member, frequent fear of a family member and alcohol problem of a family member.19 The survey scale was chosen owing its brevity and previous use in Finnish health surveys. The brevity of the scale is a valuable asset in a health survey that includes a large number of instruments. Moreover, this measure of adversities has been previously shown to be associated with CHD and depression in cross-sectional analyses and to predict disability retirement in a longitudinal sample.11 16 20 The subjects were asked to respond either ‘no’, ‘yes’ or ‘cannot say’ to each item. A binary variable (no or yes) for each adversity was created by excluding the subjects who responded “cannot say” to the adversity item from the analyses. The items were analysed separately and as a summary variable that included the adversities associated with the primary end point. The reliability of the measure of childhood adversities has been previously assessed and found to be good, because the calculated κ values of responses between 1998 and 2003 were indicating good to very good agreement (among controls 0.56–0.90 and among patients with CHD 0.59–0.77).16 The κ values were at their lowest in both groups for the item ‘severe illness of a family member’.

Disease end points

Participants' personal identification numbers (a unique number assigned to each Finnish citizen) were used to collect data on hospitalisations from the National Hospital Discharge Register as well as mortality data from the Statistics Finland Register. For the follow-up, the date and cause of hospitalisation and death for all participants who were treated in a hospital or died between 1 January 1999 and 31 December 2005 were obtained. The primary end point, based on the main diagnoses, was ischaemic heart or CVD as determined by ICD-10 codes I20–I25, I61, I63, I65, I66. Secondary end points were1 the diagnosis of acute ischaemic heart disease (I20.0, I21, I22, I24) or cerebral infarction (I63) and2 all-cause mortality.

Confounders and mediators

All background variables were measured at baseline in 1998. Because risk factors for ischaemic heart and CVD may vary according to gender,21 22 men and women were analysed separately. Age was included in the background variables as a confounder. All other variables were treated as mediators, potentially underlying the link between childhood adversities and adulthood disease. These included education (basic, secondary, lower tertiary, higher tertiary),23 24 health risk behaviours, depression, hypertension and diabetes. We assessed four behaviour-related risk factors using standard questionnaire measurements. Smoking status was measured with a variable describing current regular smoking (current/never-smoker or ex-smoker/missing information). High alcohol intake was present with a weekly self-reported consumption of beer, wine and spirits exceeding 16 drinks (≥200 g of alcohol). The body mass index, calculated from self-reported weight and height, was used to measure obesity (ie, body mass index ≥30 kg/m2). Physical activity was calculated by the Metabolic Equivalent Task index to measure sedentary life style (<2 MET hours per day).25 Symptoms of depression were measured with the Beck Depression Inventory (BDI). Depression (yes/no) was indicated by a BDI sum score of >18.26 Data on childhood adversities and background variables were based on a survey, whereas outcome measures were based on a register.

From the National Drug Reimbursement Register, kept by the Social Insurance Institution of Finland, we identified participants with hypertension, diabetes or CHD. Hypertension and diabetes were considered as potential mediators and CHD as exclusion criteria. The register contains information on people entitled to special reimbursement and the date when the special reimbursement was granted. In Finland, the national sickness insurance scheme covers the whole population and provides basic reimbursement of 42% for all medications with reimbursement confirmed by the Pharmaceuticals Pricing Board, and special medication reimbursement of 72% or 100% for certain chronic and severe diseases. Patients who apply for special reimbursement must attach a detailed medical certificate from the treating doctor, who also provides data to confirm the diagnosis. We identified all participants entitled to special reimbursements for medication for hypertension, diabetes and CHD in 1998—that is, the baseline survey year.

Exclusion criteria

We excluded from the study all participants entitled to special reimbursements for CHD, or hospitalised in 1998 owing to CHD or CVD. Thus, the remaining sample consisted of initially healthy participants in relation to the outcome.

Statistical analysis

Differences in childhood adversities as a function of sample characteristics were assessed using a χ2 test. We fitted Cox proportional hazards models to study the associations of childhood adversities with the end points and reported the hazard ratios (HRs) and their 95% CIs for men and women. Follow-up period was calculated from 1 January 1999 to the date of the diagnosis of the disease outcome, death or, for those who remained disease-free and alive, to the end of year 2005. The time-dependent interaction terms between any childhood adversity and the logarithm of the follow-up period were all non-significant (p≥0.09), confirming that the proportional hazards assumptions were justified. The proportional hazards models were adjusted for age group and, additionally, for potential mediators (education, health risk behaviours, hypertension, diabetes, or depression). A cumulative adversity score was constructed as a sum of the specific childhood adversities that were found to be associated with the primary end point. Linear trend was tested and this score was treated as a continuous variable. All the analyses were performed with the SAS 9.1.3 statistical software (SAS Institute).

Results

Of the respondents, 61% reported at least one childhood adversity. Childhood adversities were more common among those with depression and low educational level (table 1), Childhood adversities were also associated with all other baseline covariates, except sedentary lifestyle (table 1). There were small to moderate (r<0.5) correlations between the different types of childhood adversities that were all statistically significant (p<0.001), with the exception of serious illness in the family (data not shown).

Table 1

Number of participants (percentages) not exposed and exposed to childhood adversities by their baseline characteristics, the HeSSup Study, Finland, 1998–2005

During the mean follow-up of 6.9 years, 198 incident ischaemic heart or cerebrovascular events in men and 91 in women were documented. More consistently among women, the risk was higher for those reporting an exposure to childhood adversities than for the non-exposed. Table 2 shows that the age-adjusted risk of the primary end point was increased twofold in women who in their childhood had experienced financial difficulties (HR=2.13; 95% CI 1.36 to 3.32), interpersonal conflicts (1.71; 1.07 to 2.73) and longstanding illness in a family member (1.61; 1.05 to 2.45). Highest risk was found in women reporting an exposure to all three of these adversities. Their risk of disease was more than threefold that of women with none of these exposures (test for linear trend, p<0.0001). Further adjustment for education, health risk behaviours, depression, hypertension and diabetes attenuated these associations. In men, an increased 1.4-fold risk was observed only among those with a longstanding illness in a family member (1.44; 1.06 to 1.96).

Table 2

HRs with their 95% CIs for childhood adversities and incident ischaemic heart or cerebrovascular disease in men and women, the HeSSup Study, Finland, 1998–2005

Figure 1 illustrates the cumulative hazard curves of incident ischaemic heart or cerebrovascular disease by the number of childhood adversities (financial difficulties, interpersonal conflicts, severe illness in a family member) in men and women. The hazard curves for the primary disease end point among women exposed to adversities differed significantly (log-rank test, p<0.0001) from the unexposed and the difference between the groups grew as a function of time. In men, only the hazard curve for disease end point among participants with the highest exposure showed a trend in differing (log-rank test, p=0.095) from the curve of the unexposed subjects.

Figure 1

Cumulative hazard of incident ischaemic heart or cerebrovascular disease by the number of childhood adversities in men and women.

The first of the secondary analyses examined the association between childhood adversities and the occurrence of unstable angina, myocardial infarction or cerebral infarction (110 cases in men and 46 in women). In women, the age-adjusted HRs (95% CI) of these acute events were for financial difficulties 2.02 (1.06 to 3.86), for interpersonal conflicts 1.76 (0.98 to 3.16) and for longstanding illness in a family member 1.51 (0.82 to 2.76). Compared with women without any of these adversities, those reporting an exposure to one, two or three adversities had an HR of 2.29 (1.14 to 4.61), 1.29 (0.51 to 3.27) and 2.38 (0.77 to 7.40), respectively. In men, no significant associations were seen (data not shown).

The latter secondary analyses examined the association between childhood adversities and all-cause mortality. During the follow-up, 183 men and 102 women died. In both sexes, fear of a family member was associated with an increased risk of death adjusted for age (table 3). In men, an increased risk of death associated also with parental divorce, interpersonal conflicts, longstanding illness and alcohol-related problems. Adjustment for potential mediators attenuated the associations with parental divorce, interpersonal conflicts and alcohol-related problems, and the first two were no longer statistically significant.

Table 3

HRs with their 95% CIs for childhood adversities and mortality in men and women, the HeSSup Study, Finland, 1998–2005

Discussion

This is to our knowledge the first large-scale longitudinal population-based study to show an increased risk of definite CHD and CVD in subjects exposed to childhood adversities. In women, we demonstrated a dose–response relationship whereby the more adversities present, the greater the risk. The associations were observed across a range of adversities. Adjustment for education, health risk behaviours, depression, hypertension and diabetes attenuated the association, suggesting that some or all of these factors may be acting as mediators of childhood adversity. Women reported significantly more childhood adversities than men, but men experienced more CHD and CVD events making differential statistical power an unlikely source for observed gender differences in exposure-associated outcomes.

Our findings are in keeping with a previous cross-sectional study that reported a dose-dependent association between adverse childhood events and self-reported CHD after adjustment for demographic, traditional and psychological risk factors.15 The adversities measured were slightly different from ours and the study did not include separate analyses for men and women. A recent longitudinal study of Finnish war evacuees who had been separated from their parents as children during the Second World War found a twofold self-reported prevalence of doctor-diagnosed cardiovascular disease among evacuees compared with people not evacuated from the same birth cohort.27 The adversities of our study were heterogeneous, whereas the outcome measures of this study were derived from national registers.

We have previously shown that in this HeSSup study population, women and men with childhood adversities have a higher risk of depression,20 higher risk of disability retirement11 and self-reported CHD in cross-sectional analyses.16 Over all, it has been established that women are more prone to have stress-related psychiatric syndromes such as depression and anxiety disorders.28 The risk of CHD and CVD did not disappear in our study after adjusting for baseline depression or health behaviours. Therefore, other pathways are likely to explain the relationship between childhood adversities and later CHD and CVD among women.

There are no comparable longitudinal data implying differences in CHD and CVD vulnerability to long-term stress between men and women. Gender differences in the incidence of an illness can result from a combination of inborn, learnt and social factors. One explanation might lie in the differences of the hypothalamic-pituitary-adrenal (HPA) axis functions and related stress reactivity. In women the HPA axis shows greater activation during stress, and gonadal steroids seem to exert a modulatory effect on HPA-axis function. Recent evidence implies that oestrogen decreases glucocorticoid-dependent negative feedback on the HPA axis.29 Moreover, animal models have shown that females are less sensitive than males to acute stress, but adjust significantly less well than males in chronic stress situations.30 Thus, gender-dependent differences in stress response and recovery time may contribute to the differential risk of diseases between men and women.31–34

The HPA axis has an immunosuppressive effect on the inflammatory defence mechanisms of cytokines to the response from overshooting and damaging the body. Recently, an association between low-grade inflammation and a history of maltreatment has been reported.10 Inflammation has also been implicated in CHD.35 Moreover, there is evidence linking inflammation to low social status.36 The outcomes of childhood adversities are not fully independent of larger socioeconomic circumstances and on later life course factors.37 In this context, adverse childhood experiences may amplify the effects of social disadvantage, such as income level, which may account for both early and later stressors.

The greater risk among women than among men deserves further exploration. The overall CHD rate is significantly lower among premenopausal women than respective men, but the incidence among women increases soon after menopause.38 The participants in our study were relatively young, from 27 to 62 years of age at the time of the follow-up, but the association between adversities and CHD was evident even after adjusting for age. Thus, this association is unlikely to be explained by hormonal changes in women.

Methodological issues

The strengths of our study are, first, reliable register-based information on the outcomes, and second, a large nationwide population sample with a prospective study design. The Finnish hospital discharge and mortality registers provide virtually complete population-wide data on hospital discharge and mortality. These register-based diagnoses of fatal and non-fatal CHD events have been shown to be a valid indicator for hard CHD events when compared with the population-based myocardial infarction register classifying the events according to the 2003 American Heart Association definition.39

The weaknesses of this study include a relatively low baseline questionnaire response rate as well as a retrospective self-report of the childhood adversities. According to the non-response analysis, there were no significant health-related selective factors among respondents and non-respondents of the survey.18 A the linkage to register data on cardiovascular outcomes was almost complete (93%), we believe that selection bias is an unlikely explanation for our findings. Furthermore, the κ values of responses to childhood adversity items between 1998 and 2003 do not indicate a major bias.16 Our survey provided no data on lifetime income level, which might be a potential confounder for the gender differences observed, because among women the income level remains lower than among men.

There is some evidence to suggest that the childhood abuse reports by different informants, such as children as victims, their parents and teachers, may differ.40 However, severe abuse is most often well remembered,41 42 with false positive reports being probably rare. Less severe adversities may well be under-reported.42 If anything, under-reporting of the adversities should have weakened the associations we found here, not exaggerated them. Furthermore, adjustment for adulthood depression may partly lead to overcontrol, as prospective cohort studies have shown that childhood adversities may increase the risk of depression, in particular when combined with genetic vulnerability.43

Depression may have affected the reporting of childhood adversities. In this study, the respondents with depression reported childhood adversities more often than those without. However, the current literature does not indicate that this is a significant problem,44–47 and this association may reflect a true association between childhood adversities and subsequent depression risk rather than reporting bias. Likewise, research on documented adverse childhood experiences indicates that their consequences are not merely artefacts of retrospective recall.37 Further prospective studies starting from childhood are needed to examine this issue in detail.

The incidence of cardiovascular events was relatively low, from 0.4% to 0.9%, depending on gender and outcome. A longer follow-up time, to the age when the outcome incidences are supposedly higher, might perhaps show stronger associations.

Conclusions

In this prospective study of a Finnish working-age random population, experience of childhood adversities was associated with increased incident CHD and CVD and mortality, especially among women, but to a less extent men. Although further studies are needed to confirm this finding, the results emphasise the importance of early risk factors in the identification and treatment of risk groups for poor health outcomes. If confirmed, these findings suggest it would be of utmost importance to provide resources to face or avoid psychosocial risk factors in the prevention of cardiovascular disease at a population level.

References

Footnotes

  • Funding The Finnish Academy, the Yrjö Jahnsson Foundation and the Heart Research Foundation, Finland.

  • Conflicts of interest None.

  • Ethics approval This study was conducted with the approval of the Turku University Central Hospital Ethics Committee.

  • Patient consent The subjects originated from a random population sample. Agreeing to participate in the study, the subjects filled-in an informed consent form.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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