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.
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
Brendan M
BM
Everett
Sandeep
S
Bansal
Nader
N
Rifai
Julie E
JE
Buring
Paul M
PM
Ridker
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