AIM: Previous studies suggest that circulating levels of interleukin-18 (IL-18) may be prospectively related to risk of coronary heart disease (CHD) in the general population. We report new data from the largest prospective study to date, which are combined with data from all published prospective studies in a meta-analysis. METHODS: We measured baseline IL-18 levels in stored serum samples of subjects from a case-control study nested within a prospective study of 5661 men aged 40-59 years recruited from general practices in 18 British towns in 1978-1980 and followed-up for up to 16 years (median time to event 8.4 years) for fatal CHD and non-fatal myocardial infarction (595 cases, 1238 controls). RESULTS: IL-18 concentrations were strongly related to cigarette smoking, triglyceride, HDL-cholesterol (inversely) and to circulating levels of several inflammatory and haemostatic markers. Men in the top third of baseline IL-18 levels had an age-adjusted odds ratio (OR) for CHD of 1.55 (95% CI 1.21, 1.98) compared with those in the lowest third; this was reduced to 1.30 (95% CI 0.99, 1.69) after additional adjustment for vascular risk factors and 1.12 (95% CI 0.84, 1.49) after further adjustment for CRP and IL-6. In meta-analyses of CVD, associations (or effect sizes) were consistent between studies; RRs were 1.64 [corrected] (95% CI 1.48, 1.83) [corrected] after age adjustment, 1.39 (95% CI 1.25, [corrected] 1.55) after additional risk factor adjustment and 1.34 (95% CI 1.17, 1.53) [corrected] after additional adjustment for inflammatory markers. CONCLUSIONS: Circulating IL-18 is prospectively and independently associated with CVD risk.
AD - Department of Primary Care and Population Health, University College London, London NW3 2PF, UK. B.jefferis@ucl.ac.uk AN - 21481392 BT - Atherosclerosis C2 - 3146704 DA - -48412328107 DP - NLM ET - 2011/04/13 LA - eng M1 - 1 N1 - Jefferis, Barbara J M HPapacosta, OliaOwen, Christopher GWannamethee, S GoyaHumphries, Steve EWoodward, MarkLennon, Lucy TThomson, AndrewWelsh, PaulRumley, AnnLowe, Gordon D OWhincup, Peter HRG/04/003/British Heart Foundation/United KingdomRG/08/008/British Heart Foundation/United KingdomRG/08/013/25942/British Heart Foundation/United KingdomResearch Support, Non-U.S. Gov'tReviewIrelandAtherosclerosis. 2011 Jul;217(1):227-33. Epub 2011 Mar 24. N2 -AIM: Previous studies suggest that circulating levels of interleukin-18 (IL-18) may be prospectively related to risk of coronary heart disease (CHD) in the general population. We report new data from the largest prospective study to date, which are combined with data from all published prospective studies in a meta-analysis. METHODS: We measured baseline IL-18 levels in stored serum samples of subjects from a case-control study nested within a prospective study of 5661 men aged 40-59 years recruited from general practices in 18 British towns in 1978-1980 and followed-up for up to 16 years (median time to event 8.4 years) for fatal CHD and non-fatal myocardial infarction (595 cases, 1238 controls). RESULTS: IL-18 concentrations were strongly related to cigarette smoking, triglyceride, HDL-cholesterol (inversely) and to circulating levels of several inflammatory and haemostatic markers. Men in the top third of baseline IL-18 levels had an age-adjusted odds ratio (OR) for CHD of 1.55 (95% CI 1.21, 1.98) compared with those in the lowest third; this was reduced to 1.30 (95% CI 0.99, 1.69) after additional adjustment for vascular risk factors and 1.12 (95% CI 0.84, 1.49) after further adjustment for CRP and IL-6. In meta-analyses of CVD, associations (or effect sizes) were consistent between studies; RRs were 1.64 [corrected] (95% CI 1.48, 1.83) [corrected] after age adjustment, 1.39 (95% CI 1.25, [corrected] 1.55) after additional risk factor adjustment and 1.34 (95% CI 1.17, 1.53) [corrected] after additional adjustment for inflammatory markers. CONCLUSIONS: Circulating IL-18 is prospectively and independently associated with CVD risk.
PY - 2011 SN - 1879-1484 (Electronic)0021-9150 (Linking) SP - 227 EP - 33 T2 - Atherosclerosis TI - Interleukin 18 and coronary heart disease: prospective study and systematic review VL - 217 ER -