Adverse childhood and adulthood experiences and risk of new-onset cardiovascular disease with consideration of social support: a prospective cohort study

Cardiovascular diseases (CVDs) are the leading global cause of mortality and a significant contributor to disability [1]. The World Health Organization defines CVD as a group of disorders of the heart and blood vessels, including stroke, coronary heart disease, and other related conditions [2]. Recent studies have highlighted the association between adverse childhood experiences (ACEs) and a series of cardiovascular risk factors [3, 4] and events later in life [5‐7]. ACEs refer to a broad range of potentially stressful experiences during childhood and adolescence [8]. The American Heart Association (AHA) has issued scientific and policy statements recognizing the impact of ACEs on cardiometabolic health throughout the life course [9, 10]. The AHA statement proposes potential pathways that link ACEs and CVD by affecting health behaviors, such as smoking and physical inactivity, pathophysiological factors like the dysregulation of the nervous, immune system, and neuroendocrine systems, and psychological factors [10]. These pathways have been supported by a recent review [5] and several studies [11, 12].

In addition, exposure to ACEs may heighten the risk of encountering adversities and perceived burdensomeness in adulthood [13, 14]; and adverse adulthood experiences (AAEs) may act as triggers in the association between ACEs and adult health [15]. However, critical knowledge gaps remain. First, few studies have concurrently investigated the impacts of ACEs and AAEs on subsequent CVDs. Research on the interaction and joint associations of ACEs and AAEs with cardiovascular health is limited, and results are inconsistent. A recent cross-sectional study revealed that childhood adversity and adulthood stressful life events are significantly and independently linked to cardiovascular health in German adults, without interactions between childhood adversity and adulthood stressful life events [16]. In contrast, a previous longitudinal study using a single variable (i.e., adulthood neighborhood disadvantage) to represent individual-level AAEs found the combined effects of childhood psychosocial adversity and neighborhood disadvantage on incident CVD among Finnish adults [7]. Second, although AAEs may be mediators between ACEs and CVDs, few studies have constructed pathway models linking ACEs, AAEs, and subsequent CVDs, and the extent to which the overall AAEs mediate the association between ACEs and incident CVD remains to be explored. Third, it is unclear whether the findings are consistent across subpopulations of different ages and sex.

According to the social support models proposed by Cohen and Wills, good social support can directly or indirectly mitigate the negative impacts of stressful events through both its structural aspects, such as the existence of relationships, and its functional aspects, which involve perceived supports that address the needs arising from stressful events [17]. Despite this knowledge, the role of social support in mitigating the adverse effects of ACEs or AAEs on cardiometabolic health has not received sufficient attention [18, 19]. Therefore, it is hypothesized that social support may serve as a covariate or modifier in the associations of ACEs and AAEs with incident CVD. Using data from the China Health and Retirement Longitudinal Study (CHARLS) and taking into account the influence of social support, this study has three main objectives: firstly, to investigate the associations of ACEs and AAEs with incident CVD; secondly, to estimate the extent to which the overall AAEs mediate the association between ACEs and incident CVD; and finally, to explore potential interactions or joint relations of ACEs and AAEs on incident CVD.

In this cohort study of middle-aged or older adults in China, exposure to ACEs or AAEs was independently associated with an increased risk of incident CVD, and the risk of incident CVD was found to increase with an increasing number of ACE or AAE indicators. Furthermore, the association between ACEs and incident CVD was partially explained by AAEs. An additive interaction was observed between ACEs and AAEs on incident CVD, with the highest risks seen in adults exposed to at least one ACE and one AAE indicator.

Despite consistent reports linking ACEs with CVD in various cultural contexts [5‐7], there is limited research investigating the impacts of both ACEs and AAEs on incident CVD, while also considering a series of covariates, including social support. Moreover, previous studies have shown associations between ACEs and CVD risk factors such as smoking, alcohol consumption [8, 42], and depression [11, 12], but there has been a lack of focus on their confounding influences in the associations between ACEs and CVD events. After adjusting for several potential confounding variables, including CVD risk factors and social support, this study still found positive associations of ACEs and AAEs with incident CVD, with a dose–response relationship between the number of ACEs or AAEs and increased risks for both males and females. Similar positive relationships were observed between the number of ACEs or AAEs and the risks of incident heart disease and incident stroke, which are components of the investigated CVD events. These findings align with a previous retrospective cohort study using the UK biobank, which demonstrated a dose–response relationship between the number of childhood maltreatment types and incident CVD [11]. A cross-sectional study in German adults also supports these results, revealing a significant and independent association between adulthood stressful life events and cardiovascular health [16]. The present study expands on previous research by demonstrating the associations of both ACEs and AAEs with incident CVD and its subgroups (i.e., heart disease and stroke) while controlling for potential CVD risk factors and young adulthood social support. Although the potential use of interventions focused on ACE or AAE for cardiovascular health has not been tested in large randomized clinical trials, the potential reversibility of ACE or AAE consequences in adults has received attention [5]. Our findings may provide insight into the early identification of vulnerable groups and the prioritization of prevention and intervention efforts for individuals with ACE or AAE exposure to safeguard their cardiovascular health. Among the individual ACEs examined, childhood domestic violence exhibited the strongest association with incident CVD, followed by childhood exposure to natural disasters and childhood physical abuse. These specific ACEs appear to be crucial aspects that need to be considered in ACE prevention strategies.

The exact mechanism underlying the associations of ACEs or AAEs with incident CVD remains poorly understood. Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, chronic inflammatory processes, increased cardiac electrical instability, myocardial ischemia, and functional changes in the central nervous system have been suggested as potential pathophysiological effects of adverse experiences in childhood or adulthood on the development and progression of CVD events [42, 43]. In addition to the mechanisms mentioned above, previous evidence also suggests that ACEs or AAEs may predispose individuals to poor mental health and an unhealthy lifestyle, including hypertension, high serum cholesterol levels, diabetes, smoking, and obesity, which in turn, predispose individuals to CVD [5, 11, 12]. Therefore, our findings regarding the associations of ACEs or AAEs with incident CVD are physiologically plausible. Nevertheless, further evidence is needed to elucidate the underlying mechanism fully.

Prior evidence suggests AAEs may play a crucial role as a disease trigger in the relationship between ACEs and adult health [15]. The present study builds upon these findings by demonstrating the mediating role of AAEs in the association between ACEs and incident CVD. Our results indicate that the association between ACEs and incident CVD was partly explained by AAEs, highlighting the importance of this pathway in the etiology of CVD. The stress generation model may explain the mediating role of AAEs [44]. Specifically, early life stress may increase the likelihood of encountering more significant stressors in adulthood, with subsequent exposure largely responsible for any variance linked to ACEs [14, 44]. Notably, ACEs, such as neglect and abuse, may inculcate cognitive biases toward the threat, thereby fostering a heightened sense of danger, even in ambiguous circumstances [45]. These negative perceptions may increase anxiety and stress levels over the lifespan. Stressful experiences in adulthood, such as job strain and discrimination, have been linked to poorer overall health and a higher prevalence of conditions such as hypertension and stroke [16]. Importantly, our findings also provide evidence of the significance of avoiding AAEs, which may help mitigate the association between ACEs and incident CVD.

Furthermore, this study observed a significant additive interaction effect between ACEs and AAEs on incident CVD. Notably, the risk associations of AAEs with incident CVD were stronger among those exposed to at least one ACE indicator, highlighting the critical importance of preventing adversity experiences for adults, particularly among those who are more vulnerable to AAEs due to prior exposure to ACEs. These results align with a longitudinal analysis in the Finnish Public Sector, which revealed that the combined effects of childhood psychosocial adversity and adult neighborhood disadvantage increased the risk of CVD [7]. However, a separate longitudinal study in the USA found that ACEs and recent life events were independently associated with a higher level of inflammation at midlife, with no evidence of synergistic effects. Notably, elevated inflammation levels have been shown to be related to CVD [15]. Therefore, given the mixed results, these findings offer valuable insights, but definitive conclusions about the interaction effects between ACEs and AAEs on CVD cannot be drawn. Further research is needed to fully elucidate the complex relations between ACEs and AAEs on the development of CVD.

Previous evidence suggests that early life social support may facilitate the development of effective coping and emotion regulation strategies to mitigate the impact of childhood and adulthood stress, as well as reduce CVD risk factors associated with ACEs or AAEs [19]. However, our study only revealed mild buffering effects of social support during young adulthood on the negative consequences of ACEs or AAEs for CVD. Further research is needed to investigate the role of social support across different age groups, including the influence of additional forms of support such as family and friend support. It is also important to explore additional significant factors that can modify the association between ACEs or AAEs and CVD. Our findings also demonstrated that age could significantly modify the relationship between ACEs or AAEs and incident CVD. Regarding CVD components, biological sex, and age may act as modifiers in the association between ACEs and incident heart disease, while age may play a modifying role in the associations between AAEs and incident stroke. Further subgroup analysis revealed that the associations of ACEs or AAEs with incident CVD did not significantly differ between males and females. However, the associations of ACEs with incident CVD were significant only in adults under 60 years old, whereas the associations of AAEs with incident CVD were stronger in older adults compared to younger ones. Among older adults (> 60 years old), the mediating role of AAEs disappeared in the association between ACEs and incident CVD, suggesting the existence of alternative pathways linking ACEs to later health outcomes [15] and the impact of ACEs on stress reactivity may diminish with age. However, this finding could also be attributed to the fact that individuals with cardiovascular events resulting from ACEs or AAEs may have already passed away by the age of 60. Nevertheless, these findings emphasize the need for further investigation into the modifying roles of biological sex and age.

The strengths of our study include the cohort design and large sample size, which provided ample statistical power to explore the associations of ACEs and AAEs with incident CVD, while enabling mediation and subgroup analyses. Furthermore, this study comprehensively estimated the impacts of both ACEs and AAEs on subsequent CVD events, with consideration of a series of covariates including young adulthood social support. However, several limitations are worth noting. First, the information on ACEs and AAEs relied on retrospective self-reports, which may have been vulnerable to reporting and recall bias. Nevertheless, previous research has demonstrated good test–retest reliability of retrospective measurements of ACEs [25]. Second, the main analysis only summed up the cumulative numbers of ACEs or AAEs, which assumes that different types of ACEs or AAEs have equivalent effects on CVD, possibly disregarding unique information. Nonetheless, this study conducted sensitivity analyses utilizing each ACE or AAE indicator, yielding similar mediation proportion patterns. Third, the study used self-reported doctors’ diagnoses, which may have underestimated the occurrence of CVD events. Moreover, the specific data on categories of heart disease, such as heart attack and coronary heart disease, were not available for our analyses. Fourth, residual confounding remains possible despite controlling for multidimensional covariates, including demographic characteristics, health behavior factors, health status factors, young adulthood social support, and metabolic biomarkers, and causal relationships cannot be confirmed. Fifth, the study findings need to be validated by other cohort studies and randomized control trials. Sixth, although previous studies using the CHARLS dataset reported slightly lower values about the number of CVD cases/total sample size than the present study [3, 18], the low number of CVD cases/total sample size may be a concern. Seventh, it is important to note that the CHARLS dataset only provides data on young adulthood social support. However, social support across other age groups and other forms of support, such as family support and friend support, may also play a role in the associations between ACEs and AAEs with incident CVD. Eighth, in this study, the difference method was used instead of structural equation modeling to estimate the proportion of mediation by the overall AAEs in the association between ACEs and incident CVD. However, conducting specific mediation/path analysis using structural equation modeling could examine direct and indirect estimates. Moreover, the confidence intervals for the mediations have wide ranges, and further research is necessary to validate the study results regarding the mediation of AAEs on the associations between ACEs and incident CVD.

In summary, exposure to ACEs or AAEs could be associated with an increased risk of CVD among middle-aged and older adults in a dose–response manner. We also observed a modest mediation of AAEs on the association between ACEs and incident CVD. Notably, we found a significant additive interaction effect between ACEs and AAEs on the risk of incident CVD, with individuals exposed to both stressors exhibiting the highest risk. Accordingly, the findings suggest that preventing ACEs alone might not substantially reduce the risk of incident CVD later in life, and other strategies for tackling AAEs may also be needed. Therefore, a comprehensive life-course health strategy targeting the prevention of both childhood and adulthood stressors may have potential value in mitigating the risks of incident CVD. However, future randomized clinical trials are needed to confirm these conclusions.