Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: a nested case-control study.
BACKGROUND
Macrophage inhibitory cytokine-1 (MIC-1) is part of the TGF-beta superfamily. Raised concentrations of MIC-1 in serum arise in several disease states, can be detected in normal individuals, and can partly be genetically determined. We aimed to investigate whether MIC-1 has a role in atherothrombosis.


METHODS
We did a prospective, nested, case-control study in 27628 initially healthy women. Of these women, we established baseline concentrations of MIC-1 in 257 who subsequently had myocardial infarction, stroke, or died from a cardiovascular event (cases) and in 257 matched for age and smoking status, who did not report cardiovascular disease during 4-year follow-up (controls). We also assessed polymorphisms in the MIC-1 gene (MIC-1 H and MIC-1 D) in all 514 women.


RESULTS
MIC-1 concentrations were higher at baseline in women who subsequently had cardiovascular events than in those who did not (618 vs 538 pg/mL, p=0.0002). Concentrations above the 90th percentile (>856 pg/mL) were associated with a 2.7-fold increase in risk (95% CI 1.6-4.9, p=0.001). This effect was independent of traditional cardiovascular risk factors and at least additive to that of C-reactive protein. There was no significant association between MIC-1 polymorphism and vascular events.


CONCLUSIONS
MIC-1 could be a novel target for cardiovascular disease prevention.
Brown
David A
DA
Centre for Immunology, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.
Breit
Samuel N
SN
Buring
Julie
J
Fairlie
W Douglas
WD
Bauskin
Asne R
AR
Liu
Tao
T
Ridker
Paul M
PM
D002318:Cardiovascular Diseases / Q000097:blood*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D005260:Female; D055436:Growth Differentiation Factor 15; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors
D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15