Bereavement and risks of cardiovascular diseases and mortality

The loss of a significant person is a serious source of stress. Increasing evidence suggests that widowhood in middle-aged or elderly population may increase the risk of all-cause mortality and cardiovascular mortality. There is some, but still limited evidence that losing a sibling or child is linked to increased risks of certain cardiovascular diseases (CVDs), primarily ischemic heart disease (IHD) and stroke. However, knowledge regarding the link between parental death and the risk of high blood pressure (BP), IHD, and stroke is limited. Furthermore, few studies have investigated the risk of atrial fibrillation (AF) in relation to bereavement; none has examined the link between the parental or sibling loss and the risk of AF. In addition to being associated with cardiovascular mortality and incident CVDs, bereavement may also affect the prognosis of various diseases. Limited evidence suggests that psychosocial stress may have a negative impact on prognosis in heart failure (HF). It remains unclear whether there is a relationship between bereavement and poor prognosis of HF.

The overarching aim of this thesis was to advance knowledge on the association between bereavement and risks of incident CVDs and on mortality in HF. More specifically, we aimed to investigate (1) the association between the death of a parent in childhood and risk for high BP measured at age 18-20 years, as well as risk for IHD and stroke in adulthood (Studies I and II); (2) the association between death of a parent by young adulthood and risk of IHD and stroke (Study III); (3) the association between parental or sibling loss in childhood and risk of AF and to compare the impact of such losses in childhood with that in adulthood (Study IV); and (4) the association between death of a close family member (i.e., of a child, spouse/partner, grandchild, sibling, or parent) and prognosis in HF (Study V). In all five studies we also investigated if the studied associations varied by the main characteristics of the loss.

Studies I and II were based on a cohort of approximately 49,000 Swedish men born between 1949 and 1951 and conscripted in 1969/1970. We linked data collected at the time of conscription to various national registers to obtain information on parental death, diagnoses of IHD and stroke, and socioeconomic and health-related factors. We found an association between parental death in childhood and an increased risk of IHD; the adjusted hazard ratio (95% confidence interval, CI) was 1.30 (1.13-1.49). The association persisted for both maternal cardiovascular and unnatural deaths, whereas for fathers the association persisted only when he died of cardiovascular causes. The association did not differ by the participants’ age at the time of the parents’ death. The death of a parent in childhood was not linked to the risk of high BP or stroke, either in the overall analyses or in the analyses with subtypes of exposure.

Studies III and IV were binational cohort studies. Study III, comprised 3,766,918 persons who were born during 1973-1998 in Denmark and 1973-1996 in Sweden, while Study IV, comprised 6,394,975 persons born during 1973-2018 in Denmark and 1973-2014 in Sweden. We established links between several national registers to obtain information on the death of a parent or sibling; diagnosis of IHD, stroke, and AF; and sociodemographic and health-related factors. We found that those exposed to the loss of a parent had a higher risk of IHD [adjusted incidence rate ratio, IRR (95% CI):1.41 (1.33-1.51)] and stroke [adjusted IRR (95% CI): 1.30 (1.21-1.38)] than their unexposed counterparts. Such a pattern was observed for all of the studied causes of death (i.e., cardiovascular, other natural, and unnatural causes). The death of a parent or sibling, both in childhood and adulthood, was linked to an increased risk of AF [adjusted IRR (95% CI): 1.24 (1.14-1.35) and 1.24 (1.16-1.33), respectively]. Losing a parent or sibling in childhood was associated with increased AF risk only if the loss was due to CVDs or other natural causes, whereas loss in adulthood was associated with increased AF risk even for unnatural deaths. We observed no substantial differences in the risk of IHD, stroke, and AF according to fine classification of participants' age at the time of loss or relationship to the deceased.

Study V was based on a cohort of 490,527 patients with HF, recorded in the Swedish Heart Failure Registry during 2000-2018 and/or in the Swedish Patient Register during 1987-2018, with a primary diagnosis of HF. We linked data from these two registers with those from several other nationwide registers to obtain information on the death of a family member, mortality, and sociodemographic and health-related factors. We found an increased risk of mortality in HF patients affected by the death of a family member compared to non-bereaved HF patients [adjusted relative risk (95% CI): 1.29 (1.27-1.30)]. The association was found for all studied causes of death of relatives (i.e., cardiovascular, other natural, and unnatural deaths) and was somewhat more pronounced for two losses than for one loss. The risk of death following the loss of spouse was higher than following the loss of other family members. The association was strongest in the first week after loss. The risk of death was increased in case of bereavement by loss of a spouse/partner, child, a grandchild, and a sibling, but not after the death of a parent.

In conclusion, bereavement due to the loss of a parent or sibling in childhood or into young adulthood was associated with an increased risk of IHD, stroke, and AF, and bereavement due to the loss of a family member was linked to poor prognosis in HF. Loss from unnatural causes was associated with an increased risk of IHD, stroke, and in case of adulthood loss with AF and with poor prognosis of HF, suggesting possible stress-related mechanisms in these associations. Our findings underscore the importance of better support and greater attention by other family members, healthcare staff, or other potentially involved professionals to the incident cardiovascular risk for bereaved children and young adults, and the risk of dying in HF patients.

List of scientific papers

I. Chen H, Hemmingsson T, Janszky I, Rostila M, Forsell Y, Meng L, Liang Y, László KD. Death of a parent during childhood and blood pressure in youth: a population-based cohort study of Swedish men. BMJ Open. 2021;11(4):e043657.
https://doi.org/10.1136/bmjopen-2020-043657

II. Chen H, Hemmingsson T, Forsell Y, Rostila M, Janszky I, László KD. Death of a parent during childhood and the risk of ischemic heart disease and stroke in adult men. Psychosomatic Medicine. 2020;82(9):810-816.
https://doi.org/10.1097/PSY.0000000000000861

III. Chen H, Li J, Wei D, Rostila M, Janszky I, Forsell Y, Hemmingsson T, László KD. Death of a parent and the risk of ischemic heart disease and stroke in Denmark and Sweden. JAMA Network Open. 2022;5(6):e221817.
https://doi.org/10.1001/jamanetworkopen.2022.18178

IV. Chen H, Janszky I, Rostila M, Wei D, Yang F, Li J, László KD. Bereavement in childhood and young adulthood and the risk of atrial fibrillation: a population-based cohort study from Denmark and Sweden. [Submitted]

V. Chen H, Wei D, Janszky I, Dahlström U, Rostila M, László KD. Bereavement and prognosis in heart failure: A Swedish cohort study. JACC Heart Failure. 2022;10(10):753-764.
https://doi.org/10.1016/j.jchf.2022.05.005