Circulating levels of interleukin 6 soluble receptor and its natural antagonist, sgp130, and the risk of myocardial infarction.

Objective: To investigate the association between circulating levels of the soluble interleukin 6 receptor (sIL6R) and the soluble gp130 (sgp130) with myocardial infarction (MI) and to explore the potential interaction between sIL6R and sgp130 in this association.

Methods: Study population is the Stockholm Heart Epidemiology Program (SHEEP), a population-based case-control study. SIL6R (ng/mL) and sgp130 (ng/mL) levels were measured in serum samples from 682 and 664 MI cases and 1103 and 1062 controls, respectively. Odds ratios (with 95% CIs) for MI were calculated using unconditional logistic regression. We adjusted for age, sex, hospital catchment area (crude) and for hypertension, diabetes, hypercholesterolemia, body mass index and smoking (adjusted model). Synergy index (S) and attributable proportion (AP) were estimated as measures of biological interaction.

Results: Elevated concentrations of sIL6R (>75th percentile value) were associated with an increased occurrence of MI (compared to ≤75th percentile), with an adjusted OR of 1.4 (95% CI, 1.1-1.8). Very high (>90th percentile value) levels of sgp130 were associated with a reduced occurrence of MI [OR 0.7 (95% CI, 0.5-0.9)] (adjusted). There was an indication of a possible interaction between high sIL6R and low sgp130 (adjusted S score 1.7, 95% CI = 0.5-6.1; AP 0.19, 95% CI = -0.2-0.5), suggesting that low sgp130 levels may synergize with high sIL6R levels to increase risk of MI.

Conclusions: sIL6R and sgp130 had opposing associations with MI. Indeed, circulating sgp130 levels may modify the association of elevated sIL6R levels with MI.