Proinflammatory Risk Factors in Patients with Ischemic Stroke: A Systematic Review and Meta-Analysis

Ischemic stroke is a leading cause of disability worldwide, often triggered by atherothrombotic or embolic events. A growing body of evidence highlights the role of neuroinflammation as a central mechanism in post-stroke damage, influenced by modifiable systemic risk factors. Emerging evidence suggests that oxidative stress mediates the impact of several modifiable risk factors by activating redox-sensitive pathways (such as NF-κB), impairing nitric oxide bioavailability, and promoting matrix metalloproteinase activity that disrupts vascular integrity and contributes to ischemic injury. In this context, our meta-analysis examined major modifiable risk factors for ischemic stroke, with a particular focus on their shared ability to promote oxidative stress and neuroinflammatory cascades. By emphasizing these redox-dependent mechanisms, our work supports the biological plausibility of exploring antioxidant strategies as complementary approaches to mitigate stroke risk. Hypertension, diabetes, dyslipidemia, smoking, atrial fibrillation, and transient ischemic attacks all contribute to oxidative damage through mechanisms such as endothelial dysfunction, vascular inflammation, and excessive free radical exposure. We searched PubMed, PubMed Central, Web of Science, and Scopus for observational studies published within the last five years, identifying 23 studies (691,524 participants) meeting eligibility criteria. Using a random-effects model, we found significant associations between stroke risk and hypertension (OR = 1.58, 95% CI: 1.28-1.94), smoking (OR = 1.61, 95% CI: 1.13-2.28), type 2 diabetes (OR = 1.53, 95% CI: 1.29-1.81), atrial fibrillation (OR = 1.88, 95% CI: 1.28-2.75), and prior transient ischemic attack (OR = 1.62, 95% CI: 1.24-2.11). These risk factors are known to contribute to systemic inflammation, potentially exacerbating neuroinflammatory cascades post-stroke. Despite limitations such as heterogeneity and low certainty of evidence, our findings reinforce the relevance of targeting inflammation-driven risk factors in stroke prevention strategies and future research.