Patients with high levels of four blood biomarkers may be more likely to have an ischemic stroke than those with low rates of the markers, researchers reported.
In an observational study, natural logarithmic statistical transformation of markers of inflammatory, endothelial, and oxidative stress – C-reactive protein (CRP), tumor necrosis factor 2 (TNF2), total homocysteine (tHcy), and vascular endothelial growth factor (VEGF) – were each tied to a greater risk of incident ischemic stroke, Ashkan Shoamanesh, MD, of McMaster University, and colleagues reported online in Neurology.
"Identification of persons at high risk of stroke allows for development of targeted interventions to reduce the burden of stroke at the individual and population levels," study co-author Jose Romero, MD, of Boston University, told MedPage Today.
Using the biomarkers also helped better predict the risk of a stroke over the more traditionally used Framingham Stroke Risk Study, Romero said.
However, given that the study was observational, the results don't mean that elevation of these markers causes strokes, "nor do we provide thresholds for clinicians to consider increased risk," Romero noted.
Additionally, while the study doesn't suggest that these markers should be measured routinely in clinical practice, it does shed light on additional markers to identify those at a greater risk of a stroke, he said.
For their study, the researchers measured the levels of 15 biomarkers associated with inflammation in the blood of those from the Framingham Heart Study Offspring Cohort who'd never had a stroke. The 3,224 participants averaged 61 years of age at the study's onset and were observed for an average of nine years. During that period, 98 had a stroke.
In a model adjusted for age and sex, four of the 15 biomarkers were linked to an increased stroke risk, they found:
- CRP: HR 1.28, 95% CI 1.04 to 1.56
- TNFR2: HR 1.33, 95% CI 1.09 to 1.63
- tHcy: HR 1.32, 95% CI 1.11 to 1.58
- VEGF: HR 1.25, 95% CI 1.07 to 1.46
Adding the four biomarkers to the Framingham Stroke Risk Profile improved the ability to predict which patients would be at greatest risk for ischemic stroke, they reported.
They also found in exploratory analyses a significant relationship between CRP and a subtype of ischemic stroke: atherosclerotic brain infarction (HR 1.31, 95% CI 1.06 to 1.33). They also saw a relationship between cerebral embolism and both interleukin 6 (HR 1.11, 95% CI 1.06 to 1.33) and fibrinogen (HR 1.40, 95% CI 1.06 to 1.86).
The study was limited by the fact that conditions that may affect vascular and systemic inflammation, such as chronic inflammatory diseases and infections, and long-term use of medications that have anti-inflammatory properties, were unaccounted for. Also, the biomarkers were measured at single time points and not repeated over time, the researchers said.
Deepak Gulati, MD, of the Ohio State University who wasn't involved in the study, called it "preliminary" in terms of establishing any solid evidence of an association between the biomarkers and ischemic stroke, but said it "brings about this important concept that needs to be explored further."
Gulati said that biomarkers must be accurately and reproducibly measurable, clinically feasible, cost effective, and prospectively validated in randomized clinical trials.
"Biomarkers are interesting, but nothing has yet been validated in terms of an ischemic stroke," he said.
Romero said future research could abet the development of "clinically meaningful thresholds" that may be used in practice and the testing of treatments and drugs in clinical trials that incorporate these markers to assess their benefit in treatment decisions for stroke risk reduction.
In an accompanying editorial, Stephen Williams, PhD, of the University of Virginia, and Svetlana Lorenzano, MD, PhD, of Sapienza University in Rome, agreed that the study "helped refine a well-established stroke risk clinical model ... and helped enhance individual stroke risk prediction," but similarly cautioned that it "should be further assessed in prospective investigations."
As of now, added Romero, stroke prevention should continue to focus on the assessment and treatment of modifiable risk factors as suggested by current stroke prevention guidelines.
- Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College
NeurologySource Reference: Shoamanesh A, et al "Circulating biomarkers and incident ischemic stroke in the Framingham Offspring Study" Neurology 2016; 87: 1-6.
NeurologySource Reference: Williams SR, Lorenzano S "Seeking the 'holy grail' of biomarkers to improve stroke risk prediction of clinical scores" Neurology 2016; 87: 1-2.