Elevated hs-CRP Levels Linked to Higher Risk of RAO and Stroke

In a study of over 460,000 participants, researchers found that every 10mg/L increase in hs-CRP was linked to a 34% higher risk of retinal artery occlusion, 24% higher risk of ischemic stroke and 12% increased risk of transient ischemic attack. These findings suggest that hs-CRP—a marker of systemic inflammation—could play a critical role in early detection and prevention strategies for vision-threatening and cerebrovascular conditions across diverse populations. Photo: Diana Shechtman, OD. Click image to enlarge. Ischemic stroke is the second leading cause of mortality in people over age 60 and the leading cause of disability, making preventive strategies a high priority. Ongoing research into its risk factors has revealed a connection between those with retinal artery occlusion (RAO) and the likelihood of ischemic stroke due to shared cardiovascular comorbidities such as hypertension, diabetes and dyslipidemia. Another inflammatory marker identified through stroke research is high-sensitivity C-reactive protein (hs-CRP), elevated levels of which have been linked to atherosclerosis, stroke and transient ischemic attack (TIA). However, information is lacking about the role of hs-CRP in RAO, and current studies are limited to single-cohort investigations.A new study published in British Journal of Ophthalmology narrows this literature gap, demonstrating that individuals with increased levels of hs-CRP are more likely to develop RAO and stroke, positioning this as another important biomarker in patient screening efforts.Data in this cross-cohort study was collected from both the UK Biobank and the Chinese Retinal Artery Occlusion study, comprising nearly 460,000 participants with a mean age of 56 and 338 participants with a mean age of 63 years, respectively. Over a median follow-up of 12 years, researchers identified 136 cases of RAO, 3,206 cases of ischemic stroke and 1,489 TIA events in the UK Biobank. After multivariable adjustment, higher hs-CRP (per 10 mg/L) level was associated with a 34% higher risk of RAO, 24% higher risk of stroke and 12% higher risk of TIA. Furthermore, RAO patients with higher hs-CRP levels were more likely to be combined with IS (2.81 mg/L vs. 10.14 mg/L). In the Chinese cohort, the association between hs-CRP with RAO and stroke was further confirmed. Higher hs-CRP (per 1 mg/L) level was associated with increased risks of RAO (OR: 1.43) and stroke (OR: 1.13), but not with TIA. According to the authors of the paper, although this study confirms a significant association of elevated hs-CRP levels with RAO, stroke and TIA, the underlying mechanisms remain unclear. “Hs-CRP is mainly produced by liver cells under the stimulation of interleukin-6, and is known as an indicator of systemic inflammation,” wrote the authors. “It has been demonstrated that hs-CRP contributed to different stages of atherogenesis. Increased hs-CRP levels marked systemic inflammation and plaque instability, leading to plaque rupture and occlusion.” The paper goes on to note that higher hs-CRP levels “may contribute to thrombosis by inducing peripheral blood monocytes to synthesise tissue factors.” For this reason, the researchers believe that hs-CRP “may play an essential role” in the progression of RAO, ischemic stroke and TIA. “The intricate mechanisms by which hs-CRP influences these conditions warrant further investigation to deepen our understanding of their interconnectedness,” they argued.This study also looked into the timing of stroke as it relates to RAO. They found that 7.4% of patients had an ischemic stroke “within 15 days before or after” the RAO, which was higher than results of previous studies, they wrote in their BJO paper. “The possible explanation was that our research was based on a 12.2-year follow-up time study, while previous studies were almost one year or less. RAO can essentially be viewed as a form of acute [ischemic stroke], leading to retinal infarctions.”The authors note some limitations of their study, including the reliance on hospital definitions of the three conditions, which may have underestimated the true incidence. Additionally, the examination of participants’ plasma inflammatory markers was a one-time event, and may not take into account dynamic changes of hs-CRP. As stroke continues to contribute to the substantial economic and healthcare burdens in communities worldwide, the authors say this study may contribute to screening efforts and vigilant monitoring of hs-CRP levels to better identify high-risk populations and tailor prevention and control measures. “Controlling hs-CRP levels might reduce the incidence of RAO and secondary stroke,” they proposed. Click here for the journal source.  Wang Y, Zhang X, Liang A, et al. High-sensitivity C-reactive protein and risk of retinal artery occlusion and ischaemic stroke: A cross-cohort study. Br J Ophthalmology. April 22, 2025 [Epub ahead of print.]