Interleukin-18 and the risk of future cardiovascular disease among initially healthy women.
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.


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.
Everett
Brendan M
BM
The Leducq Center for Molecular and Genetic Epidemiology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, United States. beverett@partners.org
Bansal
Sandeep
S
Rifai
Nader
N
Buring
Julie E
JE
Ridker
Paul M
PM
D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis*; D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000175:diagnosis; D020382:Interleukin-18 / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors; D012907:Smoking
D020382:Interleukin-18; D002784:Cholesterol