Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: a nested case-control study

Lancet. 2002 Jun 22;359(9324):2159-63. doi: 10.1016/S0140-6736(02)09093-1.


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.

Findings: 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.

Interpretation: MIC-1 could be a novel target for cardiovascular disease prevention.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cardiovascular Diseases / blood*
  • Case-Control Studies
  • Cytokines / blood*
  • Cytokines / genetics
  • Female
  • Growth Differentiation Factor 15
  • Humans
  • Middle Aged
  • Polymorphism, Genetic
  • Prospective Studies
  • Risk Factors


  • Cytokines
  • GDF15 protein, human
  • Growth Differentiation Factor 15