Baseline depressive symptoms and stroke risk
The analysis that estimated the effect of baseline depressive symptoms on stroke risk included 10,100 individuals; 3,099 (30.7%) had elevated depressive symptoms at baseline (W1), and 545 (5.4%) had reported stroke events during the following 5-year period. The mean age of this sample was 59.6, and 5,425 (53.7%) were women (Supplementary table I). Participants with elevated depressive symptoms were more likely to be women, with a low education level, single, living in rural areas, and with heart disease.
Compared to those with no elevated depressive symptoms at baseline, participants reporting elevated depressive symptoms had a markedly increased risk of stroke incidents in model 1 (OR 1.52, 95% CI 1.27–1.81). The results were similar after adjusting for demographic characteristics in model 2 (OR 1.52, 95% CI 1.27–1.82). In model 3, after fully adjusting for age, sex, education, marital status, place of residence, smoking status, drinking frequency, BMI, hypertension, diabetes, and heart disease, individuals with elevated depressive symptoms had a higher stroke risk (OR 1.53, 95% CI 1.28–1.84) than those with no elevated depressive symptoms. There were no interactions by baseline age (P=0.95), gender (P=0.41) and place of residence (P=0.19) in fully adjusted model (Supplementary table II).
Changes in depressive symptoms and stroke risk
A total of 8,491 participants were included in the analysis of changes in depressive symptoms (Table 1). The mean age of the sample members was 59.4, 4,688 (55.2%) of them were women, and the majority were married. There were 2,612 (30.8%) and 2,852 (33.6%) participants who had a depression rating score of 10 or greater at W1 and W2, respectively, indicative of elevated depressive symptoms.
Participants with stable low/no depressive symptoms were the most commonly reported depressive symptom pattern 4,646 (54.7%), followed by the stable high group 1,619 (19.1%), recent onset group, 1,234 (14.5%), and recently remitted group, 992 (11.7%). Most of the patients with stable high depressive symptoms were women, living in rural areas with low education, single, and with heart disease.
Of all subjects with no history of stroke before W3, 430 (5.1%) had reported stroke incidents during the following 3-year period. The results of the binary logistic regression analysis are shown in Table 2. In model 1, compared to those with stable low/no depressive symptoms, those who had stable high depressive symptoms had higher probability of stroke incidents (OR 2.01, 95% CI 1.59–2.53), and recently manifested depressive symptoms were also associated with increased stroke incidents (OR 1.40, 95% CI 1.05–1.85). No significant associations were detected among the recently remitted group (OR 1.12, 95% CI 0.80–1.56). In model 2, after additional adjustment for baseline age, gender, education, marital status, and place of residence, the ORs were slightly altered, but the statistical significances remained similar. In model 3, after fully adjusting for age, gender, education, marital status, place of residence, smoking status, drinking frequency, BMI, hypertension, diabetes, and heart disease, patients with stable high and recent-onset depressive symptoms had respectively 101% (OR 2.01, 95% CI 1.58–2.56) and 39% (OR 1.39, 95% CI 1.04–1.85) higher stroke risk than did patients with stable low/no depressive symptoms. No significant associations were found among patients with remitted depressive symptoms (p > 0.05). Subgroup analyses and interaction analyses results are presented in supplementary table III. The P values for interactions assessing possible differences in effect by baseline age (0.22), gender (0.73), and place of residence (0.10) were not statistically significant.
The stable low/no group was used as the reference. The model 1 was unadjusted. The model 2 was adjusted by baseline demographic variables including age, gender, education, marital status, place of residence. The model 3 was further adjusted by smoking status, drinking frequency, body mass index, hypertension, diabetes and heart disease.
Sensitivity analyses
Subsequently, in sensitivity analyses (Supplementary table IV), where elevated depressive symptoms were defined by a higher cutoff (CESD-10 ≥ 15), participants reporting elevated depressive symptoms at baseline had a 1.51-fold higher risk of stroke compared to those with no elevated symptoms in the fully adjusted model. Stable high (OR 2.33, 95% CI 1.70–3.20) and recent onset (OR 1.60, 95% CI 1.19–2.16) depressive symptoms were statistically associated with increased stroke risks in comparison to stable low/no group. Yet no significant associations were detected between recently remitted of depressive symptoms and stroke risk (p > 0.05).