Association of Incident Stroke Risk With an IL-18-Centered Inflammatory Network Biomarker Composite.

Autor:	Martirosian RA; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Wiedner CD; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (C.D.W., R.B., J.J.H., S.S.), University of Texas Health Science Center at San Antonio., Sanchez J; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Mun KT; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Marla K; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Teran C; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Thirion M; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., Liebeskind DS; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.)., McGrath ER; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.).; HRB Clinical Research Facility, School of Medicine, University of Galway, Ireland (E.R.M.G.)., Zucker JM; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.)., Bernal R; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (C.D.W., R.B., J.J.H., S.S.), University of Texas Health Science Center at San Antonio., Beiser AS; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.).; Department of Neurology, Boston University School of Medicine, MA (A.S.B., J.J.H., S.S.).; Department of Biostatistics, Boston University School of Public Health, MA (A.S.B., J.J.H.)., DeCarli C; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.).; Department of Neurology, University of California Davis, Sacramento (C.D.C.)., Himali JJ; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (C.D.W., R.B., J.J.H., S.S.), University of Texas Health Science Center at San Antonio.; Department of Population Health Sciences (J.J.H.), University of Texas Health Science Center at San Antonio.; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.).; Department of Neurology, Boston University School of Medicine, MA (A.S.B., J.J.H., S.S.).; Department of Biostatistics, Boston University School of Public Health, MA (A.S.B., J.J.H.)., Seshadri S; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (C.D.W., R.B., J.J.H., S.S.), University of Texas Health Science Center at San Antonio.; Framingham Heart Study, MA (E.R.M.G., J.M.Z., A.S.B., C.D.C., J.J.H., S.S.).; Department of Neurology, Boston University School of Medicine, MA (A.S.B., J.J.H., S.S.)., Hinman JD; David Geffen School of Medicine, University of California Los Angeles (R.A.M., J.S., K.T.M., K.M., C.T., M.T., D.S.L., J.D.H.).
Jazyk:	angličtina
Zdroj:	Stroke [Stroke] 2024 Jun; Vol. 55 (6), pp. 1601-1608. Date of Electronic Publication: 2024 May 01.
DOI:	10.1161/STROKEAHA.123.044719
Abstrakt:	Background: A coordinated network of circulating inflammatory molecules centered on the pleotropic pro-atherogenic cytokine interleukin-18 (IL-18) is linked to cerebral small vessel disease. We sought to validate the association of this inflammatory biomarker network with incident stroke risk, cognitive impairment, and imaging metrics in a sample of the Framingham Offspring Cohort. Methods: Using available baseline measurements of serum levels of IL-18, GDF (growth and differentiation factor)-15, soluble form of receptor for advanced glycation end products, myeloperoxidase, and MCP-1 (monocyte chemoattractant protein-1) from Exam 7 of the Framingham Offspring Cohort (1998-2001), we constructed a population-normalized, equally weighted log-transformed mean Z -score value representing the average level of each serum analyte to create an inflammatory composite score (ICS5). Multivariable regression models were used to determine the association of ICS5 with incident stroke, brain magnetic resonance imaging features, and cognitive testing performance. Results: We found a significant association between ICS5 score and increased risk for incident all-cause stroke (hazard ratio, 1.48 [95% CI, 1.05-2.08]; P =0.024) and ischemic stroke (hazard ratio, 1.51 [95% CI, 1.03-2.21]; P =0.033) in the Exam 7 cohort of 2201 subjects (mean age 62±9 years; 54% female) aged 45+ years with an all-cause incident stroke rate of 6.1% (135/2201) and ischemic stroke rate of 4.9% (108/2201). ICS5 and its component serum markers are all associated with the Framingham Stroke Risk Profile score (β±SE, 0.19±0.02; P <0.0001). In addition, we found a significant inverse association of ICS5 with a global cognitive score, derived from a principal components analysis of the neuropsychological battery used in the Framingham cohort (-0.08±0.03; P =0.019). No association of ICS5 with magnetic resonance imaging metrics of cerebral small vessel disease was observed. Conclusions: Circulating serum levels of inflammatory biomarkers centered on IL-18 are associated with an increased risk of stroke and cognitive impairment in the Framingham Offspring Cohort. Linking specific inflammatory pathways to cerebral small vessel disease may enhance individualized quantitative risk assessment for future stroke and vascular cognitive impairment. Competing Interests: Disclosures C. Teran is a former University of California Log Angeles Health employee supported by National Institutes of Health funding. Dr Liebeskind is scientific advisor and on the Board of Directors of Sage Cerebrovascular Diagnostics, Inc. Dr McGrath receives grant support from the Health Research Board. Dr DeCarli is a consultant to Eisai and Novo Nordisk. Dr Himali receives grant support from NIH, the Alzheimer’s Drug Discovery Foundation, and the Alzheimer’s Association. Dr Seshadri is a consultant for Biogen and Eisai. Dr Hinman is a listed inventor on the following patents held by the Regents of the University of California that include blood measurement of the molecules included in this study: Japan Patent No. 7211626; Korea Patent No. 10-2538752; US Application 62/461,161; Canada Application 3,054,083; EPO Application 18755090.0. Dr Hinman is also the founder of Sage Cerebrovascular Diagnostics, Inc. which has an exclusive license from the Regents to commercialize diagnostic tests using these markers. The other authors report no conflicts.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu