Age and sex modify the relationship between long-term depressive symptoms and heart rate variability
N Ntlapo, R Kousovista, N van Gerwen, B W J H Brenda, M KavousiAbstract
Purpose
We examined how longitudinal depressive symptoms relate to longitudinal heart rate (HR) and heart rate variability (HRV) across the life course and whether age and sex modify these relationships.
Methods
We included 8836 participants from a large population-based study. Linear mixed-effects models using person-mean centering were applied to disentangle within-person (time-varying) and between-person effects of depressive symptoms measured with center for epidemiological studies depression (CESD) scale on heart rate (HR) and HRV metrics, standard deviation of normal to normal intervals (SDNNc), and root mean square of successive differences (RMSSDc) (corrected for HR). All models were adjusted for demographic and cardiovascular risk factors. To examine temporal directionality, we then fitted lagged linear mixed-effects models. Analyses were conducted in the full cohort and stratified by age (45-54, 55-64, 65+ years) and sex and formally tested for age × sex interaction.
Results
The mean age was 61.4 (±7.49) years, and 59% of participants were women. Overall, depression was concurrently associated with HR within-persons (β=0.33, p=0.001) but not between-persons (β=-0.22, p=0.069). No significant associations were observed for HRV metrics, SDNNc and RMSSDc. Higher depressive symptoms were associated with lower between-person differences in HR (β = -1.11%, p = 0.041) and RMSSDc (β = -4.95%, p = 0.046) among women aged 45-54. While higher depressive symptoms were associated with within-person differences in HR (β = 0.50%, p = 0.05) among women aged 55-64 and among older men ≥65 years (β = 1.38%, p = 0.004). In the lagged models, depression was significantly associated with a lower subsequent HR in the overall sample (β = -0.16, P = 0.044). Notably, age and sex jointly modified the lagged association between depression and RMSSDc (overall age × sex interaction: p=0.045), with women aged ≥65 years displaying a trend toward lower subsequent RMSSDc (β=-0.048, p=0.074).
Conclusion
The temporal relationship between depressive symptoms and autonomic function is jointly modified by sex and age. Women in midlife demonstrate concurrent autonomic differences, whereas older women may be vulnerable to delayed HRV effects. The findings recognize critical life-stage–specific windows for cardiovascular prevention in depressed individuals.depression and HRVLagged depression and HRV