TY - JOUR
T1 - Interleukin 18 and coronary heart disease
T2 - Prospective study and systematic review
AU - Jefferis, Barbara J.M.H.
AU - Papacosta, Olia
AU - Owen, Christopher G.
AU - Wannamethee, S. Goya
AU - Humphries, Steve E.
AU - Woodward, Mark
AU - Lennon, Lucy T.
AU - Thomson, Andrew
AU - Welsh, Paul
AU - Rumley, Ann
AU - Lowe, Gordon D.O.
AU - Whincup, Peter H.
N1 - Funding Information:
This work was supported by the British Heart Foundation: Professor AG Shaper established the British Regional Heart Study, which is a British Heart Foundation Research Group. PHW, AR, GDOL and SEH are supported by programme grants from the British Heart Foundation [grants RG/04/003 , RG/08/013/25942 and RG/08/008 ]. The views expressed in this paper are those of the authors and not necessarily those of the British Heart Foundation.
PY - 2011/7
Y1 - 2011/7
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 1.63 (95% CI 1.46, 1.82) after age adjustment, 1.39 (95% CI 1.24, 1.55) after additional risk factor adjustment and 1.34 (95% CI 1.17, 1.54) after additional adjustment for inflammatory markers. Conclusions: Circulating IL-18 is prospectively and independently associated with CVD risk.
AB - 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 1.63 (95% CI 1.46, 1.82) after age adjustment, 1.39 (95% CI 1.24, 1.55) after additional risk factor adjustment and 1.34 (95% CI 1.17, 1.54) after additional adjustment for inflammatory markers. Conclusions: Circulating IL-18 is prospectively and independently associated with CVD risk.
KW - Cohort
KW - Coronary heart disease
KW - Epidemiology
KW - Interleukin-18
KW - Meta-analysis
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U2 - 10.1016/j.atherosclerosis.2011.03.015
DO - 10.1016/j.atherosclerosis.2011.03.015
M3 - Article
C2 - 21481392
AN - SCOPUS:79960258060
SN - 0021-9150
VL - 217
SP - 227
EP - 233
JO - Atherosclerosis
JF - Atherosclerosis
IS - 1
ER -