April 18, 2000Circulation2,446 citationsOpen Access
Plasma Concentration of Interleukin-6 and the Risk of Future Myocardial Infarction Among Apparently Healthy Men
Key Result
Men in the highest quartile of baseline IL-6 concentration had a 2.3 times higher risk of future myocardial infarction compared to those in the lowest quartile.
Key Points
- This research aims to evaluate the relationship between interleukin-6 concentrations and the risk of myocardial infarction in apparently healthy men.
- Measured baseline plasma concentration of interleukin-6 in 202 participants who later had myocardial infarction and matched controls.
- Conducted a follow-up over 6 years to track myocardial infarction incidence.
- Compared the median IL-6 levels between groups and analyzed risk using quartiles.
- Men who had a myocardial infarction had higher median IL-6 levels (1.81 pg/mL) compared to those who did not (1.46 pg/mL).
- The relative risk of myocardial infarction increased significantly with higher quartiles of IL-6, with the highest quartile having a 2.3 times greater risk than the lowest.
- Each quartile increase in IL-6 was associated with a 38% increase in MI risk.
Study Design
Type
Cohort (n=14,916)
Blinding
null
Randomization
null
Multicenter
No
Structured PICO
Does elevated baseline IL-6 increase the risk of future myocardial infarction in apparently healthy men?
P
Population
Apparently healthy US male physicians 40 to 84 years of age with no prior history of myocardial infarction, stroke, transient ischemic attack, or cancer
I
Intervention
Elevated baseline plasma concentration of Interleukin-6 (IL-6)
C
Comparator
Lower baseline plasma concentration of Interleukin-6 (IL-6)
O
Outcome
Future myocardial infarction (MI)hard clinical
Elevated baseline levels of IL-6 in apparently healthy men are associated with a significantly increased risk of future myocardial infarction, supporting the role of inflammation in early atherogenesis.
Main Result
Effect estimate: RR 2.3 (95% CI 1.3 to 4.3)
Absolute Event Rate: 1.81% vs 1.46%
p-value: p=0.005
Limitations
- Single baseline blood sample used, limiting variation analysis.
- Non-uniform blood sample collection time may affect results.
- Based on a single baseline blood sample, unable to account for variation over time
- Blood samples were not obtained at a uniform time of day, potentially limited by diurnal variation
- Samples were stored frozen, cannot completely exclude the possibility of protein degradation
Abstract
Background —Interleukin-6 (IL-6) plays a central role in inflammation and tissue injury. However, epidemiological data evaluating the role of IL-6 in atherogenesis are sparse. Methods and Results —In a prospective study involving 14 916 apparently healthy men, we measured baseline plasma concentration of IL-6 in 202 participants who subsequently developed myocardial infarction (MI) and in 202 study participants matched for age and smoking status who did not report vascular disease during a 6-year follow-up. Median concentrations of IL-6 at baseline were higher among men who subsequently had an MI than among those who did not (1.81 versus 1.46 pg/mL; P =0.002). The risk of future MI increased with increasing quartiles of baseline IL-6 concentration ( P for trend <0.001) such that men in the highest quartile at entry had a relative risk 2.3 times higher than those in the lowest quartile (95% CI 1.3 to 4.3, P =0.005); for each quartile increase in IL-6, there was a 38% increase in risk ( P =0.001).This relationship remained significant after adjustment for other cardiovascular risk factors, was stable over long periods of follow-up, and was present in all low-risk subgroups, including nonsmokers. Although the strongest correlate of IL-6 in these data was C-reactive protein ( r =0.43, P <0.001), the relationship of IL-6 with subsequent risk remained after control for this factor ( P <0.001). Conclusions —In apparently healthy men, elevated levels of IL-6 are associated with increased risk of future MI. These data thus support a role for cytokine-mediated inflammation in the early stages of atherogenesis.
Expert Takes1 quote
“In practice, hs-CRP has been used to characterize residual inflammatory risk with levels ≥2 mg/L as an entry criterion for multiple trials. However, IL-6 is more specific and predictive, although it lacks a clinically validated cutpoint.”
ACC Journal ScanView source