BACKGROUND AND OBJECTIVES: High serum IL-6 is a major risk factor for cardiovascular disease (CVD) in the general population. This cytokine is substantially increased in patients with CKD, but it is still unknown whether the link between IL-6 and CVD in CKD is causal in nature. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cohort of 755 patients with stages 2-5 CKD, consecutively recruited from 22 nephrology units in southern Italy, this study assessed the relationship of serum IL-6 with history of CVD, as well as with incident cardiovascular (CV) events (mean follow up±SD, 31±10 months) and used the functional polymorphism (-174 G/C) in the promoter of the IL-6 gene to investigate whether the link between IL-6 and CV events is causal. RESULTS: In adjusted analyses, serum IL-6 above the median value was associated with history of CVD (P<0.001) and predicted the incidence rate of CV events (hazard ratio, 1.66; 95% confidence interval [95% CI], 1.11 to 2.49; P=0.01). Patients homozygous for the risk allele (C) of the -174 G/C polymorphism had higher levels of IL-6 than did those with other genotypes (P=0.04). Homozygous CC patients more frequently had a history of CVD (odds ratio, 2.15; 95% CI, 1.15 to 4.00; P=0.02) as well as a 87% higher rate of incident CV events (hazard ratio, 1.87; 95% CI, 1.02 to 3.44; P=0.04) compared with other genotypes. CONCLUSIONS: In patients with stages 2-5 CKD, high serum IL-6 is associated with history of CVD and predicts incident CV events. The parallel relationship with history of CVD and incident CV events of the -174 G/C polymorphism in the IL-6 gene suggests that IL-6 may be causally involved in the high CV risk in this population.
BACKGROUND AND OBJECTIVES: High serum IL-6 is a major risk factor for cardiovascular disease (CVD) in the general population. This cytokine is substantially increased in patients with CKD, but it is still unknown whether the link between IL-6 and CVD in CKD is causal in nature. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cohort of 755 patients with stages 2-5 CKD, consecutively recruited from 22 nephrology units in southern Italy, this study assessed the relationship of serum IL-6 with history of CVD, as well as with incident cardiovascular (CV) events (mean follow up±SD, 31±10 months) and used the functional polymorphism (-174 G/C) in the promoter of the IL-6 gene to investigate whether the link between IL-6 and CV events is causal. RESULTS: In adjusted analyses, serum IL-6 above the median value was associated with history of CVD (P<0.001) and predicted the incidence rate of CV events (hazard ratio, 1.66; 95% confidence interval [95% CI], 1.11 to 2.49; P=0.01). Patients homozygous for the risk allele (C) of the -174 G/C polymorphism had higher levels of IL-6 than did those with other genotypes (P=0.04). Homozygous CC patients more frequently had a history of CVD (odds ratio, 2.15; 95% CI, 1.15 to 4.00; P=0.02) as well as a 87% higher rate of incident CV events (hazard ratio, 1.87; 95% CI, 1.02 to 3.44; P=0.04) compared with other genotypes. CONCLUSIONS: In patients with stages 2-5 CKD, high serum IL-6 is associated with history of CVD and predicts incident CV events. The parallel relationship with history of CVD and incident CV events of the -174 G/C polymorphism in the IL-6 gene suggests that IL-6 may be causally involved in the high CV risk in this population.
Authors: Nancy S Jenny; Russell P Tracy; Malcolm S Ogg; Le Ahn Luong; Lewis H Kuller; Alice M Arnold; A Richey Sharrett; Steve E Humphries Journal: Arterioscler Thromb Vasc Biol Date: 2002-12-01 Impact factor: 8.311
Authors: Madhumathi Rao; Daqing Guo; Mary C Perianayagam; Hocine Tighiouart; Bertrand L Jaber; Brian J G Pereira; Vaidyanathapuram S Balakrishnan Journal: Am J Kidney Dis Date: 2005-02 Impact factor: 8.860
Authors: Jennifer K Pai; Tobias Pischon; Jing Ma; JoAnn E Manson; Susan E Hankinson; Kaumudi Joshipura; Gary C Curhan; Nader Rifai; Carolyn C Cannuscio; Meir J Stampfer; Eric B Rimm Journal: N Engl J Med Date: 2004-12-16 Impact factor: 91.245
Authors: Bernhard Schieffer; Tina Selle; Andres Hilfiker; Denise Hilfiker-Kleiner; Karsten Grote; Uwe J F Tietge; Christian Trautwein; Maren Luchtefeld; Christian Schmittkamp; Sylvia Heeneman; Mat J A P Daemen; Helmut Drexler Journal: Circulation Date: 2004-11-22 Impact factor: 29.690
Authors: Paula Jerrard-Dunne; Matthias Sitzer; Paul Risley; Donata A Steckel; Alexandra Buehler; Stefan von Kegler; Hugh S Markus Journal: Stroke Date: 2003-02 Impact factor: 7.914
Authors: William R Zhang; Amit X Garg; Steven G Coca; Philip J Devereaux; John Eikelboom; Peter Kavsak; Eric McArthur; Heather Thiessen-Philbrook; Colleen Shortt; Michael Shlipak; Richard Whitlock; Chirag R Parikh Journal: J Am Soc Nephrol Date: 2015-04-08 Impact factor: 10.121
Authors: Carmine Zoccali; Raymond Vanholder; Ziad A Massy; Alberto Ortiz; Pantelis Sarafidis; Friedo W Dekker; Danilo Fliser; Denis Fouque; Gunnar H Heine; Kitty J Jager; Mehmet Kanbay; Francesca Mallamaci; Gianfranco Parati; Patrick Rossignol; Andrzej Wiecek; Gerard London Journal: Nat Rev Nephrol Date: 2017-04-24 Impact factor: 28.314
Authors: Lene Ryom; Jens D Lundgren; Mike Ross; Ole Kirk; Matthew Law; Philippe Morlat; Eric Fontas; Colette Smit; Christoph A Fux; Camilla I Hatleberg; Stéphane de Wit; Caroline A Sabin; Amanda Mocroft Journal: J Infect Dis Date: 2016-08-02 Impact factor: 5.226
Authors: Jair Munoz Mendoza; Tamara Isakova; Xuan Cai; Liz Y Bayes; Christian Faul; Julia J Scialla; James P Lash; Jing Chen; Jiang He; Sankar Navaneethan; Lavinia Negrea; Sylvia E Rosas; Matthias Kretzler; Lisa Nessel; Dawei Xie; Amanda Hyre Anderson; Dominic S Raj; Myles Wolf Journal: Kidney Int Date: 2016-12-22 Impact factor: 10.612
Authors: Jia Sun; Jonas Axelsson; Anna Machowska; Olof Heimbürger; Peter Bárány; Bengt Lindholm; Karin Lindström; Peter Stenvinkel; Abdul Rashid Qureshi Journal: Clin J Am Soc Nephrol Date: 2016-06-08 Impact factor: 8.237
Authors: Stanislas Werfel; Georg Lorenz; Bernhard Haller; Roman Günthner; Julia Matschkal; Matthias C Braunisch; Carolin Schaller; Peter Gundel; Stephan Kemmner; Salim S Hayek; Christian Nusshag; Jochen Reiser; Philipp Moog; Uwe Heemann; Christoph Schmaderer Journal: Sci Rep Date: 2021-04-29 Impact factor: 4.379
Authors: Susana Rocha; Maria João Valente; Susana Coimbra; Cristina Catarino; Petronila Rocha-Pereira; José Gerardo Oliveira; José Madureira; João Carlos Fernandes; Maria do Sameiro-Faria; Vasco Miranda; Luís Belo; Alice Santos-Silva; Elsa Bronze-da-Rocha Journal: Sci Rep Date: 2021-07-20 Impact factor: 4.379