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Juonala M, Pulkki-Råback L, Elovainio M, et al. Childhood Psychosocial Factors and Coronary Artery Calcification in AdulthoodThe Cardiovascular Risk in Young Finns Study. JAMA Pediatr. 2016;170(5):466–472. doi:10.1001/jamapediatrics.2015.4121
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There is increasing evidence supporting the importance of psychosocial factors in the pathophysiology of atherosclerotic disease. They have been shown to be associated with the population attributable risk for myocardial infarction.
To determine if a score of favorable childhood psychosocial factors would be associated with decreased coronary artery calcification in adulthood.
Design, Setting, and Participants
The analyses were performed in 2015 using data gathered in 1980 and 2008 within the longitudinal Cardiovascular Risk in Young Finns Study. The data source consisted of 311 individuals who had psychosocial factors measured at ages 12 years to 18 years and coronary artery calcification measured 28 years later in adulthood. The summary measure of psychosocial factors in childhood comprised measures of socioeconomic factors, emotional factors, parental health behaviors, stressful events, self-regulation of the child, and social adjustment of the child.
Main Outcomes and Measures
Coronary artery calcification at ages 40 years to 46 years.
Of the 311 participants, 48.2% were men. Of the participants, 55 (17.7%) had some calcium observed in their coronary arteries. A 1-SD increase in a favorable summary score of childhood psychological factors was associated with an adulthood coronary artery calcification probability of 0.85 (95% CI, 0.76-0.95) (P = .006). This inverse relationship remained significant after adjustment for age, sex, and conventional childhood risk factors (0.85; 95% CI, 0.74-0.97; P = .02) or for age, sex, adulthood conventional cardiovascular risk factors, socioeconomic status, social support, and depressive symptoms (0.83; 95% CI, 0.71-0.97; P = .02).
Conclusions and Relevance
In this longitudinal study, we observed an independent association between childhood psychosocial well-being and reduced coronary artery calcification in adulthood. A positive childhood psychosocial environment may decrease cardiovascular risk in adulthood and may represent a potentially modifiable risk determinant.
Atherosclerosis is a complex disease. While dyslipidemia, hypertension, diabetes, and smoking are major risk determinants, there are several other causal and modifying factors.1 There has been increasing interest in the importance of psychosocial factors.2 For example, depression is associated with increased risk for incident clinical atherosclerotic disease and increased mortality rate in those with existing cardiovascular disease.3 In addition to longitudinal studies, case-control studies have demonstrated that psychosocial factors are powerful contributors to the population attributable risk for myocardial infarction.4 These factors include depression, general stress, financial stress, life events, and locus of control with a combined population attributable risk of 29%.4 Socioeconomic status, which is strongly correlated with psychological health,5 is also an important cardiovascular risk factor.6
Coronary disease and stroke become clinically evident in middle age or later, but atherosclerosis develops beginning early in life. For example, in the Bogalusa Heart Study,7 childhood lipid profile and blood pressure were shown to be associated with early atherosclerotic lesions observed in coronary arteries present at the mean age of 18 years. Therefore, it is possible to examine the presence of atherosclerotic changes in the vasculature among younger, asymptomatic persons. Coronary artery calcification (CAC) detected by computed tomography (CT) is a validated predictive marker of subclinical atherosclerosis.8,9 Coronary artery calcification is found more frequently in advanced coronary lesions10; conversely, the absence of detectable CAC in asymptomatic patients implies that the presence of atherosclerotic plaque is unlikely.10 Coronary artery calcification has been associated with incident coronary heart disease in different populations beyond that provided by conventional risk factors.9,11
In a 2015 study, we observed that a constellation of several favorable psychosocial factors was associated with an improved American Heart Association Ideal Cardiovascular Health Index in adulthood.12 Prior research has focused on single psychosocial predictors, although the combined effect of multiple psychosocial factors may be more important.13 Evidence has suggested a graded association where several psychosocial exposures (multiple adversities occurring at the same time) have superior predictive power for cardiovascular events.14-17 However, to our knowledge, no study has examined whether these factors in childhood are associated with adulthood CAC. Such knowledge would be important for primary prevention. Specifically, establishing factors that might protect against pathogenic development of CAC would be in keeping with goals that aim to improve the cardiovascular health of the entire population.18
In this study, we examined whether a summary measure of favorable psychosocial factors that can reflect both the presence of positive factors (eg, high parental caregiving nurturance) and the absence of negative factors (eg, absence of previously diagnosed parental mental disorder) in childhood could be associated with lower risk of CAC in adulthood. The study cohort was a subsample of the longitudinal Cardiovascular Risk in Young Finns Study (N = 311, mean [SD] baseline age, 14.5 [2.4] years) with data on psychosocial factors in childhood and CAC measurements performed 28 years later.
Question: Is a score of favorable childhood psychosocial factors associated with descreased coronary artery calcification in adulthood?
Findings: A favorable summary measure of childhood psychological factors was significantly inversely associated with the prevalence of any coronary artery calcification in adulthood.
Meaning: A positive childhood psychosocial environment may decrease cardiovascular risk in adulthood and may represent a potentially modifiable risk determinant.
The Cardiovascular Risk in Young Finns Study is a multicenter follow-up study of atherosclerosis precursors in Finnish children and adolescents. The first cross-sectional survey was conducted in 1980, when 3596 participants aged 3 years, 6 years, 9 years, 12 years, 15 years, and 18 years were randomly chosen from the 5 study areas. Thereafter, follow-up studies were performed at 3- to 9-year intervals. In 2008, a cardiac CT study to measure CAC was conducted for 589 individuals, then 40 to 46 years of age. This was a convenience sample; the 3 oldest cohorts (aged 12 years, 15 years, and 18 years at baseline) from 3 centers with a possibility to perform CAC imaging were invited (n = 711, attendance rate 80%).19 For this study, 311 individuals with complete data on childhood psychosocial factors in 1980 and CAC imaging performed in 2008 were included. The study was approved by the ethics committees of Helsinki University Hospital, Kuopio University Hospital, Oulu University Hospital, Tampere University Hospital, and Turku University Hospital. All participants and/or their parents gave written informed consent.
We assessed 6 psychosocial factors proposed as central components of childhood psychosocial environment in previous literature.20,21 These were socioeconomic environment, emotional environment, parental health behaviors, stressful events, self regulation, and social adjustment of the child. These factors were assessed by parents using standardized questionnaires at the baseline examination in 1980.12 We built the 6 psychosocial factors from binary variables, where 1 stands for favorable and 0 for less than favorable. The cutoff points were based on previous evidence and theoretical knowledge as described in detail elsewhere.12
Favorable socioeconomic factors score consisted of 4 components: upper white collar occupation (1 point); academic/college degree (1 point); family income in highest 25% (1 point); and occupational stability as indicated by absence of unemployment spells, retirement, and/or long-term medical leave (1 point).
Favorable emotional family environment score consisted of 4 components. The first was absence of diagnosed parental mental disorder (1 point). The second was high parental caregiving nurturance, measured using a 7-item scale (α = .70) previously used in this data set. A reply “very often” to all items gave 1 point. The third component was high parental life satisfaction, measured using a 3-item scale. A positive reply to all 3 items gave 1 point. Fourth, reasonable alcohol use was included because of evidence indicating that unhealthy drinking is harmful to emotional development.22 Parents reporting intoxication “never or at maximum 3 times per year” were classified as reasonable users (1 point).
Optimal health behaviors of the parents were reported independently by each parent. Because we had no data on parental diet, we used body mass index of more than 30.0 (calculated as weight in kilograms divided by height in meters squared) as a proxy of excess energy intake (0, obese and 1, nonobese). Other health behaviors were nonsmoker (1 point) and regular physical activity (1 point for exercise at least weekly).
Lack of stressful events included events that may threaten a child’s sense of stability and continuity. The stressful events were moving residence, change of school, parental divorce or separation, death of a family member, and serious disease in the family. Nonpresence of each event gave 1 point.
Self-regulatory behavior of the participant consisted of 2 scales, 1 measuring high self-control and the other measuring high aggression control. Predictive validity of both scales has been established previously.23,24 The self-control scale consisted of 1 question where children described as being very controlled “always or most of the time” received 1 point. Aggression control (α = .60) was measured with 6 items, each giving 1 point. The total score was formed by combining scores from self-control and aggression control.
Social adjustment was assessed by a question about parental worry about the child’s adjustment (1 point) and parental evaluation of the child’s general level of adjustment (1 point). Our previous work has shown that these questions are associated with outcomes that are theoretically related to social adjustment.23
Summary scores have become common in research on psychosocial factors.13,25 The rationale for using scores comes from child development theory, which posits that it is not any particular risk factor but rather the number of risk factors in a child’s background that leads to adverse developmental outcomes.26 These notions have further been validated in studies showing that multiple rather than single exposures have worse cardiometabolic outcomes.12,15,16 Therefore, 6 psychosocial factors were combined to form a favorable psychosocial factors score (summary score). Each psychosocial factor score was first standardized because the psychosocial factors differed in scale range, and there was no hypothesis to weigh any factor relative to others. Thus, the formula for the score was: socioeconomic environment (z score) + emotional environment (z score) + parental health behaviors (z score) + stressful events (z score) + self-regulation (z score) + social adjustment (z score) = favorable psychosocial factors score.
Height and weight were measured, and body mass index was calculated as weight in kilograms divided by height in meters squared.2 In childhood, blood pressure was measured from the brachial artery using a standard mercury sphygmomanometer. In adulthood, a random-zero mercury sphygmomanometer was used. The average of 3 measurements was used in analysis. For the determination of serum lipid levels, venous blood samples were drawn after an overnight fast both in childhood and adulthood. These analyses as well as measurements of adulthood glucose levels were performed with standard enzymatic methods. Information on smoking habits (own and parental) was obtained with a questionnaire. In adulthood, questionnaires were used to gather data on participants’ socioeconomic status (annual income), perceived social support,27 and depressive symptoms.28
Computed tomographic scans were performed at 3 study locations in Finland: Turku, Tampere, and Kuopio. The scans were performed with a GE Discovery 64-slice CT/positron emission tomography device (GE Healthcare) (Turku), a Philips Brilliance 64-slice CT device (Philips Medical Systems) (Tampere), and a Siemens Somatom Sensation 16-slice CT device (Siemens Healthcare) (Kuopio). Coronary artery calcification scores were calculated using the Agatston method for each coronary artery.29 The coefficient of variation for intraobserver measurements was 4%. Absence of CAC was defined as an Agatston score of 0 and presence of CAC as an Agatston score of 1 or greater.19 An imaging phantom with deposits of known calcium concentration was also scanned twice using 3 projections at all of the study centers, and the calcium scores from these scans were compared. The coefficient of variation between scans was 3.9%.
Standardized probabilities and 95% CIs for the association between childhood psychosocial factors and the presence of any CAC in adulthood were estimated using logistic regression with a logit link. Owing to skewed distribution of the calcium score variable, Spearman nonlinear correlation analyses were used to analyze the associations with continuous CAC scoring in adulthood. The analyses were performed both unadjusted and adjusted with age, sex, and conventional cardiovascular risk factors in childhood and adulthood. Analyses were performed using SAS software, version 9.2 (SAS Institute). Statistical significance was inferred at a 2-tailed P value of .05 or less.
The baseline characteristics of 311 study participants are shown in Table 1. The prevalence of any CAC was 17.7% (n = 55). Total CAC scores of 1 to 10, 11 to 100, and greater than 100 were measured in 28 (9.0%), 20 (6.5%), and 7 (2.2%) participants. In attrition analyses, the study group was younger (14.5 years vs 15.1 years, P = .005) and their smoking prevalence was lower (7.4% vs 13.0%, P = .03) when compared with those individuals with CAC measurements but had incomplete data on baseline psychosocial factors. In age- and sex-adjusted analyses, there were statistically significant differences between these groups in high-density lipoprotein cholesterol (P = .03) and triglyceride (P < .001) levels.
As shown in Table 2, the childhood psychosocial factor score was inversely associated with the prevalence of any CAC in adulthood. This relation remained significant after adjustments for age, sex, and conventional childhood risk factors. In addition, in an analysis adjusted for age, sex, and adulthood risk factors including body mass index, lipids, blood pressure, glucose, smoking, annual income, social support, and depressive symptoms, the inverse relation remained significant (0.83; 95% CI, 0.71-0.97; P = .02). Of the individual childhood psychosocial factors, self-regulatory behavior was inversely associated with adult CAC (Table 2).
In analyses performed separately for different coronary artery regions, there was a significant inverse association between childhood psychosocial score and CAC in the left anterior descending artery (Table 3). This inverse relationship was also independent of adulthood risk factors (0.79; 95% CI, 0.64-0.97; P = .03).
Childhood psychosocial factor score was also inversely associated with the adult CAC score. In analyses adjusted for age, sex, and childhood or adulthood risk factors, Spearman correlation coefficients were r = −0.14, P = .01 and r = −0.12, P = .04, respectively.
These longitudinal data suggest that adverse childhood psychosocial factors are associated with CAC 28 years after the baseline evaluation. The composite score of 6 psychosocial factors (socioeconomic environment, emotional environment, parental health behaviors, stressful events, self-regulation of the child, and social adjustment of the child) was related to CAC even after adjustment for age, sex, and conventional cardiovascular risk factors in childhood. Moreover, the association with CAC was independent of adulthood cardiovascular and psychosocial factors.
These findings extend previous data highlighting the importance of a positive childhood psychosocial environment with regard to adult health outcomes. Studies from the Young Finns cohort and from the Collaborative Perinatal Project in the United States have reported associations with favorable cardiovascular risk factor status in adulthood.12,17 Existing evidence suggests a graded association where several psychosocial exposures are associated with greater risk for cardiovascular diseases. Such a graded association has been shown for adverse cardiometabolic profiles15,17,30 and incident cardiovascular disease.14,16 However, most studies have measured childhood exposures retrospectively. Concerning CAC, in the longitudinal Coronary Artery Risk Development in Young Adults study,31-33 it has been shown that hostility and socioeconomic position in early adulthood (at ages 18-30 years) are related with later CAC. In our study, we observed that for every favorable 1-SD change in childhood psychosocial factors score, the probability of CAC in adulthood was decreased by 15% in a model adjusted with childhood risk factors and 17% when adjusted with adulthood risk factors. These findings suggest that favorable psychosocial environment in childhood is associated independently with lower risk of later atherosclerosis.
There are several possible mechanistic explanations for these results. In the Coronary Artery Risk Development in Young Adults study, early adulthood psychosocial factors have been shown to relate to metabolic functioning and inflammatory process.34-36 We have previously reported a relationship between positive childhood psychosocial factors and better cardiovascular health in adulthood, as measured using the American Heart Association Ideal Cardiovascular Health Index.12 A 2012 model approach suggests that positive psychological experiences may increase restorative processes (eg, healthy behaviors) leading to optimal cardiovascular health.37 At the same time, adverse psychosocial factors (or lack of positive factors) may promote deteriorative processes (eg, inflammation) that increase the risk for cardiac diseases.37 In animal models, several psychosocial factors, such as stress, social status, aggressiveness, responsiveness to psychological challenge, and the stability of the social environment, have been associated with atherosclerotic changes in vasculature.38 As a next step, research should attempt to identify the mechanistic pathways whereby early-life psychosocial exposures lead to vascular changes in humans.
From the clinical perspective, our findings underscore the need for increased awareness of promoting positive psychosocial health in childhood. Because data on many of the factors used in the summative score could be readily gathered at diverse health service encounters, these data might be used in targeted family interventions for primary prevention, especially in those at greatest risk.
This study has key strengths, particularly the longitudinal analysis of a population-representative cohort over 3 decades. We were also able to take into account the effects of major cardiovascular risk factors. We acknowledge some unavoidable limitations, including that we only had data on the complete set of childhood psychosocial factors among a subcohort from the Young Finns study. This may compromise the statistical power and increase the possibility of type II error, so the findings should be interpreted cautiously until further studies can confirm our results. Our assessment for childhood psychosocial factors was developed for this specific study 3 decades ago and is not a current standard measure, limiting the possibility of direct comparison of our findings with other studies. However, we have obtained predictive validity by showing that our summary measure is associated with conceptually relevant outcomes such as mental health39 and cardiometabolic biomarkers12 in adulthood. Although the psychosocial score specifically developed for this study was nonstandard, the 6 psychosocial facets chosen to represent childhood factors were theoretically sound,26 representing childhood domains that have gained robust evidence as being important for future cardiometabolic outcomes.12,16,17 Another limitation was that the assessments were based on self-reports and asked from parents alone, which can induce bias if the parent has not been able to make balanced judgments. The advantage of using parental assessments was that they were made independently of the child outcomes, thus eliminating common-rater variance. Altogether, we acknowledge that our measurement battery had several limitations, but it nevertheless provided an estimate of a wider range of childhood factors than most studies. Furthermore, summary binary scores have the advantages of being parsimonious. They make no assumptions about the relative strengths of multiple risk factors or their collinearity, and they enable testing of additive effects over a range of exposures.13 Because the study cohort is composed of young adults, we were not able to study associations with cardiovascular events. Instead, we have used CT measures of CAC as a validated marker of significant atherosclerosis. This method has been widely used in clinical studies where it predicts cardiovascular outcomes independently of conventional risk factors.9 Moreover, in a 2014 American College of Cardiology Foundation Appropriate Use Criteria Task Force statement,40 CT measurement of CAC was mentioned as the modality to assess the extent of subclinical atherosclerosis to be used for the risk assessment of coronary disease among certain groups of asymptomatic individuals.40 Finally, because study participants were predominantly white, the results cannot necessarily be generalized to other racial/ethnic groups.
We have shown an independent association between childhood psychosocial factors and CAC in adulthood. This finding suggests that favorable childhood psychosocial environment may decrease cardiovascular risk in adulthood. Strategies that aim to optimize psychological well-being may be beneficial in reducing adult cardiovascular disease.
Corresponding Author: Markus Juonala, MD, PhD, Department of Medicine, University of Turku, Kiinamyllynkatu 4-8, Turku, PO Box 52, 20521 Turku, Finland (firstname.lastname@example.org).
Published Online: March 14, 2016. doi:10.1001/jamapediatrics.2015.4121.
Author Contributions: Drs Juonala and Pulkki-Råback had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Juonala, Pulkki-Råback, Elovainio, Sabin, Saraste, Hutri-Kähönen, Viikari, Raitakari.
Acquisition, analysis, or interpretation of data: Juonala, Pulkki-Råback, Elovainio, Hakulinen, Magnussen, Burgner, Hare, Hartiala, Ukkonen, Saraste, Kajander, Kähönen, Rinta-Kiikka, Laitinen, Kainulainen, Viikari, Raitakari.
Drafting of the manuscript: Juonala, Pulkki-Råback, Elovainio, Sabin, Hartiala, Saraste, Hutri-Kähönen, Raitakari.
Critical revision of the manuscript for important intellectual content: Pulkki-Råback, Hakulinen, Magnussen, Sabin, Burgner, Hare, Hartiala, Ukkonen, Saraste, Kajander, Hutri-Kähönen, Kähönen, Rinta-Kiikka, Laitinen, Kainulainen, Viikari, Raitakari.
Statistical analysis: Juonala, Pulkki-Råback, Hakulinen, Raitakari.
Obtained funding: Juonala, Pulkki-Råback, Laitinen, Raitakari.
Administrative, technical, or material support: Saraste, Hutri-Kähönen, Kähönen, Rinta-Kiikka, Kainulainen, Raitakari.
Study supervision: Saraste, Viikari, Raitakari.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was financially supported by the Academy of Finland (grants 126925, 121584, 124282, 129378, 117797, 265977, and 41071); the Social Insurance Institution of Finland; the Turku University Foundation; Paulo Foundation (Dr Juonala); Paavo Nurmi Foundation (Dr Juonala); Juho Vainio Foundation (Drs Juonala and Pulkki-Råback); Signe and Ane Gyllenberg Foundation (Dr Pulkki-Råback); Sigrid Juselius Foundation (Dr Juonala); Maud Kuistila Foundation (Dr Juonala); research funds from the Kuopio, Turku, and Tampere University Hospitals; the Finnish Foundation of Cardiovascular Research (Dr Juonala); the Finnish Medical Foundation (Dr Juonala); the Orion-Farmos Research Foundation; the Finnish Cultural Foundation and the Bothnia Welfare Coalition for Research and Knowledge through grants from the Regional Council of Ostrobothnia; the Vaasa Hospital District; the City of Vaasa; the University of Vaasa; and European Regional Development Fund (Dr Pulkki-Råback). Dr Magnussen holds a National Health and Medical Research Council Early Career Fellowship (APP1037559). Dr Sabin holds a National Health and Medical Research Council Health Professional Training Fellowship (APP1012201). Dr Burgner holds a National Health and Medical Research Council Senior Research Fellowship (APP1064629) and an honorary National Heart Foundation Future Leader Fellowship (100369). Dr Hare holds a National Health and Medical Research Council Practitioner Fellowship (APP628399). Research at Murdoch Childrens Research Institute is supported by the Victorian Government's Operational Infrastructure Support Program.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.