Stroke. 2001;32:2575-2579
doi: 10.1161/hs1101.098151
doi: 10.1161/hs1101.098151
(Stroke. 2001;32:2575.)
© 2001 American Heart Association, Inc.
Original Contributions |
Plasma Concentration of C-Reactive Protein and Risk of Ischemic Stroke and Transient Ischemic Attack
The Framingham Study
From the National Heart, Lung, and Blood Institute’s Framingham Study (P.A.W., C.S.K., M.K.-H., P.W.F.W.), Framingham, Mass, and the Departments of Neurology (N.S.R., P.A.W., C.S.K., M.K.-H.), Mathematics and Statistics (H.S., R.B.D), Epidemiology and Biostatistics (J.M.M.), Biochemistry (C.F.), and Medicine (P.W.F.W.), Boston University School of Medicine, Boston, Mass.
Correspondence to Philip A. Wolf, MD, Neurological Epidemiology and Genetics, Boston University School of Medicine, 715 Albany St, B-608, Boston, MA 02118-2526. E-mail pawolf{at}bu.edu
Background—— The role of C-reactive protein (CRP) as a novel plasma marker of atherothrombotic disease is currently under investigation. Previous studies have mostly related CRP to coronary heart disease, were often restricted to a case-control design, and failed to include pertinent risk factors to evaluate the joint and net effect of CRP on the outcome. We related plasma CRP levels to incidence of first ischemic stroke or transient ischemic attack (TIA) in the Framingham Study original cohort.
Methods—— There were 591 men and 871 women free of stroke/TIA during their 1980 to 1982 clinic examinations, when their mean age was 69.7 years. CRP levels were measured by using an enzyme immunoassay on previously frozen serum samples. Analyses were based on sex-specific CRP quartiles. Risk ratios (RRs) were derived, and series of trend analyses were performed.
Results—— During 12 to 14 years of follow-up, 196 ischemic strokes and TIAs occurred. Independent of age, men in the highest CRP quartile had 2 times the risk of ischemic stroke/TIA (RR=2.0, P=0.027), and women had almost 3 times the risk (RR=2.7, P=0.0003) compared with those in the lowest quartile. Assessment of the trend in risk across quartiles showed unadjusted risk increase for men (RR=1.347, P=0.0025) and women (RR=1.441, P=0.0001). After adjustment for smoking, total/HDL cholesterol, systolic blood pressure, and diabetes, the increase in risk across CRP quartiles remained statistically significant for both men (P=0.0365) and women (P=0.0084).
Conclusions—— Independent of other cardiovascular risk factors, elevated plasma CRP levels significantly predict the risk of future ischemic stroke and TIA in the elderly.
Key Words: atherosclerosis • C-reactive protein • inflammation • ischemic stroke • risk factors • TIA
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 S. B. Kritchevsky, M. Cesari, and M. Pahor Inflammatory markers and cardiovascular health in older adults Cardiovasc Res, May 1, 2005; 66(2): 265 - 275. [Abstract] [Full Text] [PDF]
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 B. J. Nicklas, T. You, and M. Pahor Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training Can. Med. Assoc. J., April 26, 2005; 172(9): 1199 - 1209. [Abstract] [Full Text] [PDF]
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A. Slowik, A. Borratynska, W. Turaj, J. Pera, T. Dziedzic, D. A. Figlewicz, M. Betlej, T. Krzyszkowski, R. Czepko, and A. Szczudlik {alpha}1-Antichymotrypsin Gene (SERPINA3) A/T Polymorphism as a Risk Factor for Aneurysmal Subarachnoid Hemorrhage Stroke, April 1, 2005; 36(4): 737 - 740. [Abstract] [Full Text] [PDF]
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J. Genius, T. Dong-Si, A. P. Grau, and C. Lichy Postacute C-Reactive Protein Levels Are Elevated in Cervical Artery Dissection Stroke, April 1, 2005; 36(4): e42 - e44. [Abstract] [Full Text] [PDF]
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 Q. Wang, X. Zhu, Q. Xu, X. Ding, Y. E. Chen, and Q. Song Effect of C-reactive protein on gene expression in vascular endothelial cells Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1539 - H1545. [Abstract] [Full Text] [PDF]
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 E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw Biochemical risk markers: a novel area for better prediction of renal risk? Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508. [Full Text] [PDF]
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H.-H. S. Oei, I. M. van der Meer, A. Hofman, P. J. Koudstaal, T. Stijnen, M. M.B. Breteler, and J. C.M. Witteman Lipoprotein-Associated Phospholipase A2 Activity Is Associated With Risk of Coronary Heart Disease and Ischemic Stroke: The Rotterdam Study Circulation, February 8, 2005; 111(5): 570 - 575. [Abstract] [Full Text] [PDF]
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L. Iacoviello, A. Di Castelnuovo, M. Gattone, A. Pezzini, D. Assanelli, R. Lorenzet, E. Del Zotto, M. Colombo, E. Napoleone, C. Amore, et al. Polymorphisms of the Interleukin-1{beta} Gene Affect the Risk of Myocardial Infarction and Ischemic Stroke at Young Age and the Response of Mononuclear Cells to Stimulation In Vitro Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 222 - 227. [Abstract] [Full Text] [PDF]
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S. P. Fortmann, E. Ford, M. H. Criqui, A. R. Folsom, T. B. Harris, Y. Hong, T. A. Pearson, D. Siscovick, F. Vinicor, and P. F. Wilson CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: Report From the Population Science Discussion Group Circulation, December 21, 2004; 110(25): e554 - e559. [Abstract] [Full Text] [PDF]
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P. W.F. Wilson CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: Ability of Inflammatory Markers to Predict Disease in Asymptomatic Patients: A Background Paper Circulation, December 21, 2004; 110(25): e568 - e571. [Abstract] [Full Text] [PDF]
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M. Diomedi, A. Pietroiusti, M. Silvestrini, B. Rizzato, L. M. Cupini, F. Ferrante, A. Magrini, A. Bergamaschi, A. Galante, and G. Bernardi CagA-positive Helicobacter pylori strains may influence the natural history of atherosclerotic stroke Neurology, September 14, 2004; 63(5): 800 - 804. [Abstract] [Full Text] [PDF]
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E. C. Suarez C-Reactive Protein Is Associated With Psychological Risk Factors of Cardiovascular Disease in Apparently Healthy Adults Psychosom Med, September 1, 2004; 66(5): 684 - 691. [Abstract] [Full Text] [PDF]
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T. T. Fung, M. J. Stampfer, J. E. Manson, K. M. Rexrode, W. C. Willett, and F. B. Hu Prospective Study of Major Dietary Patterns and Stroke Risk in Women Stroke, September 1, 2004; 35(9): 2014 - 2019. [Abstract] [Full Text] [PDF]
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S. I. Sokol, E. L. Portnay, J. P. Curtis, M. A. Nelson, P. R. Hebert, J. F. Setaro, and J. M. Foody Modulation of the renin-angiotensin-aldosterone system for the secondary prevention of stroke Neurology, July 27, 2004; 63(2): 208 - 213. [Abstract] [Full Text] [PDF]
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M. K. Rutter, J. B. Meigs, L. M. Sullivan, R. B. D'Agostino Sr, and P. W.F. Wilson C-Reactive Protein, the Metabolic Syndrome, and Prediction of Cardiovascular Events in the Framingham Offspring Study Circulation, July 27, 2004; 110(4): 380 - 385. [Abstract] [Full Text] [PDF]
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P. M Ridker, P. W.F. Wilson, and S. M. Grundy Should C-Reactive Protein Be Added to Metabolic Syndrome and to Assessment of Global Cardiovascular Risk? Circulation, June 15, 2004; 109(23): 2818 - 2825. [Abstract] [Full Text] [PDF]
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 B. J Nicklas, W. Ambrosius, S. P Messier, G. D Miller, B. W. Penninx, R. F Loeser, S. Palla, E. Bleecker, and M. Pahor Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial Am. J. Clinical Nutrition, April 1, 2004; 79(4): 544 - 551. [Abstract] [Full Text] [PDF]
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 T. You, D. M. Berman, A. S. Ryan, and B. J. Nicklas Effects of Hypocaloric Diet and Exercise Training on Inflammation and Adipocyte Lipolysis in Obese Postmenopausal Women J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1739 - 1746. [Abstract] [Full Text] [PDF]
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F. O'Rourke, N. Dean, N. Akhtar, and A. Shuaib Current and future concepts in stroke prevention Can. Med. Assoc. J., March 30, 2004; 170(7): 1123 - 1133. [Abstract] [Full Text] [PDF]
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V. Janardhan, P. A. Wolf, C. S. Kase, J. M. Massaro, R. B. D'Agostino, C. Franzblau, and P. W.F. Wilson Anticardiolipin Antibodies and Risk of Ischemic Stroke and Transient Ischemic Attack: The Framingham Cohort and Offspring Study Stroke, March 1, 2004; 35(3): 736 - 741. [Abstract] [Full Text] [PDF]
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L. Mascitelli and F. Pezzetta Anti-inflammatory Effect of Physical Activity Arch Intern Med, February 23, 2004; 164(4): 460 - 460. [Full Text] [PDF]
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P.J. Kelly, J.P. Kistler, V.E. Shih, R. Mandell, N. Atassi, M. Barron, H. Lee, S. Silveira, and K.L. Furie Inflammation, Homocysteine, and Vitamin B6 Status After Ischemic Stroke Stroke, January 1, 2004; 35(1): 12 - 15. [Abstract] [Full Text] [PDF]
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G. J. Blake, N. Rifai, J. E. Buring, and P. M Ridker Blood Pressure, C-Reactive Protein, and Risk of Future Cardiovascular Events Circulation, December 16, 2003; 108(24): 2993 - 2999. [Abstract] [Full Text] [PDF]
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M. Schillinger, M. Exner, J. Amighi, W. Mlekusch, S. Sabeti, H. Rumpold, O. Wagner, and E. Minar Joint Effects of C-Reactive Protein and Glycated Hemoglobin in Predicting Future Cardiovascular Events of Patients With Advanced Atherosclerosis Circulation, November 11, 2003; 108(19): 2323 - 2328. [Abstract] [Full Text] [PDF]
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 S. L. Seliger, D. L. Gillen, D. Tirschwell, H. Wasse, B. R. Kestenbaum, and C. O. Stehman-Breen Risk Factors for Incident Stroke among Patients with End-Stage Renal Disease J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2623 - 2631. [Abstract] [Full Text] [PDF]
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M. Di Napoli Editorial Comment--C-Reactive Protein and Vascular Risk in Stroke Patients: Potential Use for the Future Stroke, October 1, 2003; 34(10): 2468 - 2470. [Full Text] [PDF]
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J. F. Arenillas, J. Alvarez-Sabin, C. A. Molina, P. Chacon, J. Montaner, A. Rovira, B. Ibarra, and M. Quintana C-Reactive Protein Predicts Further Ischemic Events in First-Ever Transient Ischemic Attack or Stroke Patients With Intracranial Large-Artery Occlusive Disease Stroke, October 1, 2003; 34(10): 2463 - 2468. [Abstract] [Full Text] [PDF]
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P. J. Lindsberg and A. J. Grau Inflammation and Infections as Risk Factors for Ischemic Stroke Stroke, October 1, 2003; 34(10): 2518 - 2532. [Abstract] [Full Text] [PDF]
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M. Chandalia, A. V. Cabo-Chan Jr, S. Devaraj, I. Jialal, S. M. Grundy, and N. Abate Elevated Plasma High-Sensitivity C-Reactive Protein Concentrations in Asian Indians Living in the United States J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3773 - 3776. [Abstract] [Full Text] [PDF]
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T. B. Ledue and N. Rifai Preanalytic and Analytic Sources of Variations in C-reactive Protein Measurement: Implications for Cardiovascular Disease Risk Assessment Clin. Chem., August 1, 2003; 49(8): 1258 - 1271. [Abstract] [Full Text] [PDF]
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J. J. Cao, C. Thach, T. A. Manolio, B. M. Psaty, L. H. Kuller, P. H.M. Chaves, J. F. Polak, K. Sutton-Tyrrell, D. M. Herrington, T. R. Price, et al. C-Reactive Protein, Carotid Intima-Media Thickness, and Incidence of Ischemic Stroke in the Elderly: The Cardiovascular Health Study Circulation, July 15, 2003; 108(2): 166 - 170. [Abstract] [Full Text] [PDF]
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