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Stroke. 2014 Apr;45(4):979-87. doi: 10.1161/STROKEAHA.113.002289. Epub 2014 Mar 13.

High-sensitivity C-reactive protein and interleukin-6-dominant inflammation and ischemic stroke risk: the northern Manhattan study.

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From the Department of Epidemiology, Mailman School of Public Health, New York, NY (J.M.L., M.S.V.E.); Departments of Neurology (Y.P.M., M.S.V.E.) and Pathology (K.M.L., S.S.), Columbia University College of Physicians and Surgeons, New York, NY; Division of Biostatistics, Mailman School of Public Health, New York, NY (M.C.P., K.C.); Departments of Neurology, Epidemiology, and Human Genetics, Miller School of Medicine, University of Miami, FL (R.L.S.); and Gertrude H. Sergievsky Center, Columbia University, New York, NY (M.S.V.E.).



Interleukin-6 (IL-6) is a proinflammatory cytokine with known autoregulatory feedback mechanisms. We hypothesized that elevated high-sensitivity C-reactive protein (hsCRP) relative to IL-6 confers an increased risk of ischemic stroke (IS), and low hsCRP relative to IL-6 a decreased risk, for individuals in the prospective, multiethnic, population-based Northern Manhattan Study (NOMAS).


Serum hsCRP and IL-6 were measured in NOMAS participants at baseline. We created a trichotomized predictor based on the dominant biomarker in terms of quartiles: hsCRP-dominant, IL-6-dominant, and codominant groups. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for the association between inflammatory biomarker group status and risk of incident IS.


Of 3298 participants, both hsCRP and IL-6 were available in 1656 participants (mean follow-up, 7.8 years; 113 incident IS). The hsCRP-dominant group had increased risk of IS (adjusted hazard ratio, 2.62; 95% confidence interval, 1.56-4.41) and the IL-6-dominant group had decreased risk (adjusted hazard ratio, 0.38; 95% confidence interval, 0.18-0.82) when compared with the referent group, after adjusting for potential confounders. Model fit was improved using the inflammation-dominant construct, over either biomarker alone.


In this multiethnic cohort, when hsCRP-quartile was higher than IL-6 quartile, IS risk was increased, and conversely when IL-6 quartiles were elevated relative to hsCRP, IS risk was decreased. Construct validity requires confirmation in other cohorts.


biomarkers; inflammation; ischemic stroke; prevention and control

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