Abstract 16298: Higher Genetic Risk for Neuroticism Heightens Cardiovascular Risk Related to Chronic Sleep Deprivation

Introduction: Chronic sleep deprivation associates with an increased risk of Major Adverse Cardiovascular Events (MACE), in part via heightened stress-related neural mechanisms. Similarly, increased polygenic risk score for neuroticism (nPRS), a measure linked to stress-sensitivity, associates with greater activity in stress-related neural pathways.

Hypothesis: We hypothesized that higher nPRS increases the MACE risk associated with chronic sleep deprivation.

Methods: A total of 9,619 participants (median age 65 years, 46% male) from the Mass General Brigham Biobank were studied. nPRS was assessed. Sleep deprivation was defined as either a short sleep duration (<7 hours/night) or a diagnosis of a sleep disorder (e.g., insomnia, sleep apnea). Sleep duration and disorders, MACE incidence, and cardiovascular risk factors were assessed using health questionnaires and International Classification of Disease codes. Logistic regression models were employed to evaluate the association between sleep deprivation and MACE and the presence of an interaction.

Results: During a median (Interquartile range) of 4.9 (4.1-5.9) years of follow-up, 807 (8.3%) individuals experienced MACE. Among individuals with higher nPRS (≥median), sleep deprivation associated with a two-fold increase in MACE risk (odds ratio [OR] [95% confidence interval (CI)]: 2.283 [1.929, 2.703], p<0.001*) compared to individuals with lower nPRS (<median) (OR [95%CI]: 1.632 [1.390, 1.917], p<0.001*; Table 1 ) with a significant interaction observed (p=0.010*). A similar trend was observed in a sensitivity analysis that excluded sleep apnea (p-interaction 0.074).

Conclusions: Our findings suggest that a high nPRS doubles the MACE risk associated with sleep deprivation. Further research is warranted to elucidate the underlying mechanisms driving this relationship.