Allostatic Load in Parents and Offspring: Sex Differences and Intergenerational Effects on Cardiovascular Disease-Free Survival

Abstract

Background: Allostatic load (AL), a measure of cumulative stress-related physiological dysregulation, predicts the onset of chronic diseases. We investigated the relationship between AL and cardiovascular disease (CVD)-free survival in parents and offspring, including sex-specific differences.

Methods: The analysis consisted of 6145 offspring-mother-father trios derived from the Framingham Heart Study. Clinically defined cutoffs from 9 physiological biomarkers across biological systems were used to generate composite AL score. Assessments of the associations of AL with CVD-free survival were conducted using Kaplan-Meier plots, Irwin's restricted means, and Cox proportional hazards regression models.

Results: Over a 47-year period, parents and offspring experienced 1832 and 1060 incident CVD events, respectively. Parents exhibited a notably higher prevalence of high AL (29.5%) and CVD incidence rate (17.2 per 1000 person-years) compared with offspring (13.2% and 8.9, respectively, both P < .001). High parental AL was associated with 30% higher incident CVD risk in offspring, with maternal AL biomarkers being more predictive of offspring CVD risk than paternal. Parents and offspring with low AL lived 12.5 and 13.4 years longer without CVD, respectively, compared with those with high AL. The hazards of incident CVD were highest in daughters with high AL, up to 2.8 times (hazard ratio, 2.83; 95% confidence interval, 1.71-4.67), with similar risk observed in sons and parents.

Conclusion: Parental AL is associated with offspring CVD risk, with maternal AL biomarkers having a stronger association. This highlights the critical role of parental and, more importantly, maternal health in CVD risk management and broader public health strategies.