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Continuous Long-Term Depressive Symptoms May Increase Stroke Risk

In comparison to those with consistently low depressive symptoms, those with consistently high, fluctuating, and increasing depressive trajectories had 18% to 31% higher hazard of developing incident stroke.

Findings from the Health and Retirement Study showed that those with depressive symptom trajectories characterized by consistently high symptoms are at an increased risk for stroke onset; however, decreasing symptom trajectories over time did not show an increased stroke risk.

In the main analysis, compared with individuals with consistently low depressive symptoms—the reference group—individuals with consistently high depressive symptoms had a higher risk for incident stroke (adjusted HR, 1.18; 95% CI, 1.02-1.36). Similarly, individuals with increasing (adjusted HR, 1.31; 95% CI, 1.10-1.57) and fluctuating (adjusted HR, 1.21; 95% CI, 1.01-1.46) depressive symptoms had a higher risk for incident stroke compared with the reference group.

After years of similar research focusing on a single time point, lead investigator Yenee Soh, ScD, SM, post-doctoral research fellow, Kaiser Permanente Northern California Division of Research, and colleagues, aimed to examine the relationship between depressive symptom trajectories and risk of incident over multiple time points. To do so, they used the 8-item Center for Epidemiologic Studies Depression scale at 4 consecutive timepoints from 1998 to 2004, with incident stroke assessed over a subsequent 10-year period from 2006 to 2016.

The study included 12,520 Americans aged at least 50 years old who were defined as either highly or lowly depressed based on whether they had 3 or more symptoms on the scale. Individuals were then assigned to 5 predefined trajectories based on their scores at each time point (consistently low, decreasing, fluctuating, increasing, and consistently high). The association of depressive symptom trajectories with risk of incident stroke was then analyzed using Cox regression models, with adjustment for demographics, health behaviors, and health conditions.

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During the 10 years of follow-up, 1434 incident strokes were recorded. Among participants, the majority (67.4%; n = 8439) had consistently low depressive symptoms over time. When comparing between-group differences of high vs low symptoms, those with consistently high symptoms had lower average levels of education (less than high school: 47.7% [n = 768] vs 20.7% [n = 1743]) and were less likely to be married (53.3% [n = 858] vs 73.3% [n = 6189]). Of the different predefined trajectories, those with decreasing depressive symptoms were the only group to not have a significantly different risk of incident stroke in comparison to the reference group (adjusted HR, 1.02; 95% CI, 0.84-1.24).

"Contrary to our hypothesis, we noted that the hazard for the decreasing depressive symptom trajectory group was not substantially different from those with consistently low depressive symptoms," Soh et al wrote. "Taken together, our results suggest that repeated occurrences of elevated depressive symptoms increase stroke risk, perhaps through accumulated cardiovascular damage over time. However, with sufficient time for recovery (ie, a period of repeated low depressive symptoms), even individuals who have experienced high depressive symptoms may not be at increased risk for stroke."

In the study, no evidence of effect modification by sex, nor race and ethnicity, were observed on the interactions between depressive symptom trajectories and incident stroke. Additionally, the 6 sensitivity analyses showed that the findings were robust to different exposure classifications, were not largely attenuated by health behaviors and conditions nor largely affected by loss to follow-up, although some attenuated associations for incident stroke with consistently high and fluctuating trajectories were evident.

1. Soh Y, Tiemeier H, Kawachi I, Berkman LF, Kubzansky LD. Eight-year depressive symptom trajectories and incident stroke: a 10-year follow-up of the HRS (Health and Retirement Study). Stroke. Published online May 23, 2022. doi:10.1161/STROKEAHA.121.037768