Mortality among twin individuals exposed to loss of a co-twin

Abstract

Background Although the death of a child, sibling or spouse has been associated with elevated risk of mortality, less is known about the survival of twin siblings exposed to a co-twin loss. Methods In a Swedish population-based sibling-matched cohort, we compared the mortality of 5548 twin individuals who lost their co-twin between 1932 and 2011 with that of 27 740 age-matched and sex-matched twin individuals without such a loss and 6772 full siblings of these exposed twin individuals. Cox regression models were used to estimate the hazard ratios (HRs) of all-cause and cause-specific mortality. Results We found increased risk of all-cause mortality among twin individuals exposed to a co-twin loss compared with matched unexposed twin individuals (HR = 1.30, 95% CI: 1.18–1.43) and their full siblings (HR = 1.10, 95% CI: 0.96–1.27) after adjusting for multiple covariates. The all-cause mortality risk was greater for loss of a co-twin due to unnatural deaths (HR = 1.54, 95% CI: 1.17–2.03) than natural deaths (HR = 1.26, 95% CI: 1.14–1.40). For cause-specific mortality, co-twin loss was associated with a higher risk of unnatural deaths both among twin individuals who lost their co-twin due to unnatural deaths (HR = 1.98, 95% CI: 1.27–3.10) and those whose loss was due to natural deaths (HR = 1.48, 95% CI: 1.07–2.06). The risk elevations were generally stronger for loss of a monozygotic co-twin than loss of a dizygotic co-twin. Conclusion Loss of a co-twin, especially a monozygotic co-twin, was associated with increased mortality, particularly of unnatural causes, among the surviving twin individuals. The excess mortality is likely attributable to both shared disease susceptibility within the twin pair and the adverse health sequelae of bereavement.

Sibling Death in Childhood and Early Adulthood and Risk of Early-Onset Cardiovascular Disease

“…Considering different causes of sibling death, we found that individuals experiencing sibling loss due to CVD had a higher CVD risk, which supports the hypothesis that common genetic and environmental cardiovascular risk factors that clustered in families are likely to be an important explanation for the association between bereavement and CVD . Nevertheless, we also observed an increased risk of CVD if the sibling died of a non-CVD cause, which suggests an independent role of stress-related mechanisms between sibling death and CVD incidence .…”

“…[9][10][11][12][29][30][31] Nevertheless, we also observed an increased risk of CVD if the sibling died of a non-CVD cause, which suggests an independent role of stress-related mechanisms between sibling death and CVD incidence. [9][10][11][12][29][30][31] Psychological stress following bereavement could activate acute stress responses, which may lead to changes in brain stress-responsive neurocircuitry and then stimulate peripheral physiological responses, including the autonomic nervous system response, hypothalamic-pituitary-adrenal responses, and sterile inflammation. [38][39][40] These stress responses would lead to pathophysiological…”

“…To our knowledge, this is the first population-based study to offer comprehensive insights into the association between sibling death and risk of overall and type-specific CVD incidence during childhood, adolescence, and young adulthood. Prior studies have predominantly focused on sibling death and its subsequent association with mortality, including all-cause mortality, suicide, and mortality from fatal stroke and MI . Among them, 2 Swedish studies including participants aged 40 to 69 years during 1981 to 2002 found that the loss of an adult sibling was associated with 11% to 31% increased risks of mortality from fatal stroke and MI .…”

“…42 In addition, twinship is often considered the closest relationship due to a higher degree of relatedness. 31 Surviving elder or twin siblings may experience more intense grief, potentially leading to unusual psychophysiological states and abnormal cardiovascular health outcomes. 31,43 The increased risks persisted over the follow-up period, with the highest risk of CVD occurring within the first year after bereavement.…”

“…31 Surviving elder or twin siblings may experience more intense grief, potentially leading to unusual psychophysiological states and abnormal cardiovascular health outcomes. 31,43 The increased risks persisted over the follow-up period, with the highest risk of CVD occurring within the first year after bereavement. Our finding was consistent with those previous studies that the risks of AF, acute MI, hemorrhagic stroke, and heart failure were the highest immediately after the death of a child or a partner.…”