OBJECTIVE: Elevated levels of interleukin (IL)-18 have been implicated in the development of atherosclerosis in animals. Data in humans are less clear, and data in women are particularly scarce. METHODS AND RESULTS: In a prospective nested case-control study of initially healthy women, we measured baseline plasma IL-18 levels in 253 participants who subsequently developed cardiovascular disease (CVD) and in 253 healthy age- and smoking-matched controls. IL-18 levels were higher at baseline among those who developed CVD (274.1pg/mL versus 233.8pg/mL, P<0.001), and were associated with future CVD (relative risk (RR) for highest versus lowest quartile 2.53; 95% CI, 1.47-4.35, P<0.001). While that risk was attenuated after adjustment for traditional cardiovascular risk factors (RR 1.60; 95% CI, 0.77-3.34, P=0.13), those with IL-18 levels at or above a threshold of the 90th percentile (442pg/mL) remained at elevated risk after adjustment (RR 2.40; 95% CI, 1.05-5.56, P=0.04). Levels of IL-18 above this threshold modify the fully adjusted risk of future CVD conferred by elevated levels of total cholesterol (P(interaction)=0.02). CONCLUSIONS: In this population of apparently healthy women, IL-18 levels associate with increased risk of cardiovascular disease, but that risk is attenuated in models adjusting for traditional cardiovascular risk factors. Very high levels of IL-18 interact with hypercholesterolemia to alter CVD risk.
OBJECTIVE: Elevated levels of interleukin (IL)-18 have been implicated in the development of atherosclerosis in animals. Data in humans are less clear, and data in women are particularly scarce. METHODS AND RESULTS: In a prospective nested case-control study of initially healthy women, we measured baseline plasma IL-18 levels in 253 participants who subsequently developed cardiovascular disease (CVD) and in 253 healthy age- and smoking-matched controls. IL-18 levels were higher at baseline among those who developed CVD (274.1pg/mL versus 233.8pg/mL, P<0.001), and were associated with future CVD (relative risk (RR) for highest versus lowest quartile 2.53; 95% CI, 1.47-4.35, P<0.001). While that risk was attenuated after adjustment for traditional cardiovascular risk factors (RR 1.60; 95% CI, 0.77-3.34, P=0.13), those with IL-18 levels at or above a threshold of the 90th percentile (442pg/mL) remained at elevated risk after adjustment (RR 2.40; 95% CI, 1.05-5.56, P=0.04). Levels of IL-18 above this threshold modify the fully adjusted risk of future CVD conferred by elevated levels of total cholesterol (P(interaction)=0.02). CONCLUSIONS: In this population of apparently healthy women, IL-18 levels associate with increased risk of cardiovascular disease, but that risk is attenuated in models adjusting for traditional cardiovascular risk factors. Very high levels of IL-18 interact with hypercholesterolemia to alter CVD risk.
Authors: F Vidal-Vanaclocha; G Fantuzzi; L Mendoza; A M Fuentes; M J Anasagasti; J Martín; T Carrascal; P Walsh; L L Reznikov; S H Kim; D Novick; M Rubinstein; C A Dinarello Journal: Proc Natl Acad Sci U S A Date: 2000-01-18 Impact factor: 11.205
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Authors: Norbert Gerdes; Galina K Sukhova; Peter Libby; Rebecca S Reynolds; James L Young; Uwe Schönbeck Journal: J Exp Med Date: 2002-01-21 Impact factor: 14.307
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Authors: Barbara J M H Jefferis; Olia Papacosta; Christopher G Owen; S Goya Wannamethee; Steve E Humphries; Mark Woodward; Lucy T Lennon; Andrew Thomson; Paul Welsh; Ann Rumley; Gordon D O Lowe; Peter H Whincup Journal: Atherosclerosis Date: 2011-03-24 Impact factor: 5.162