Association between baseline high-sensitive C-reactive protein, homocysteine levels, and post-stroke depression among stroke patients: a systematic review, meta-analysis, and meta-regression

Background: Post-stroke depression (PSD) is a prevalent neuropsychiatric sequelae following stroke, often associated with diminished functional recovery and heightened mortality risk. Emerging evidence suggests neuroinflammation, triggered in response to stroke events, may be instrumental in precipitating PSD.

Aim: This study aims to assess the significance of high-sensitivity C-reactive protein (Hs-CRP) and homocysteine (Hcy) in post-stroke individuals with PSD.

Methods: We systematically searched all electronic databases from inception until May 30, 2023. Outcomes were reported as standard mean difference (SMD), and their corresponding 95% confidence interval (95% CI).

Results: A total of 12 studies with 3,230 patients were included in this study. The mean age of the overall cohort was 65.7 years, and patients with PSD were observed to be older than patients without PSD (68.3 years versus 63.1 years). We observed a higher female prevalence in the PSD group (44.4% versus 40.7%). PSD patients were more likely to be widowed (19.4% versus 8.4%) and more likely to have a family history of psychiatric disorder (11.3% versus 4.9%) compared to non-PSD patients. We also observed that patients with PSD had higher levels of baseline Hs-CRP [SMD 0.16, (95% CI 0.08 to 0.25), p<0.001], and Hcy [SMD 0.14, (95% CI 0.05 to 0.22), p<0.001] than patients without PSD. Meta-regression analysis did not reveal any effect modifier for higher Hs-CRP in the study group, however, history of widowhood was a significant effect modifier when assessing Hcy levels between the two groups (coefficient 1.998, p=0.038).

Conclusion: Baseline levels of Hs-CRP and Hcy were significantly higher in patients with PSD, highlighting the role of recognizing demographic and biochemical markers in understanding the complexities of post-stroke depression.