Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men.

By P. Ridker, N. Rifai, MR Stampfer, C. Hennekens. Circulation, 2000

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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.

Subfields: Cardiology and Cardiovascular Medicine, Epidemiology, Immunology

View Paper: https://www.semanticscholar.org/paper/76b53adc143c8b0cbaca485ba12c8c059c039ae1

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Citations in the corpus

Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. (2003, background): “diovascular disease (29, 35) and insulin resistance (23)”
Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women's Health Initiative observational study. (2002, background): “…men and women 4-10 and among patients with stable angina pectoris, 21 acute coronary ischemia, 22-24 or a history of MI. 25 Similar associations between baseline elevations of IL-6 with incident vascular events 26 and cardiovascular mortality 27 have been documented among healthy individuals.”
Inflammatory mediators in the elderly. (2004, background): “Accordingly, IL-6 was a predictor of myocardial infarcts in healthy middle-aged men (Ridker et al., 2000).”
Long-Term Interleukin-6 Levels and Subsequent Risk of Coronary Heart Disease: Two New Prospective Studies and a Systematic Review (2008, background): “Updated Meta-analysis We identified 17 relevant studies [8–21] (including the two current studies, ten newly identified studies [8–13,17,19–21], and five studies [14–16,18] included in the previous published review [22]; flow chart in Figure 1).”
Determinants of Long-Term Survival After Major Surgery and the Adverse Effect of Postoperative Complications (2005, background): “Elevated levels of IL 6 and CRP relate to myocardial infarction(41) and can also predict myocardial infarction in asymptomatic men.(42) Myocardial events per se appear to be prominent determinants of long-term survival.”
Obesity and the role of adipose tissue in inflammation and metabolism. (2006, background): “Elevated IL-6 concentration is a predictor for development of type 2 diabetes and for myocardial infarction (61, 62).”
Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms. (2002, background): “A number of studies have shown that in medically healthy adults, depression is accompanied by higher circulating levels of interleukin-6, C-reactive protein, and tumor necrosis factor-a [57,58], all of which are inflammatory risk markers for cardiac morbidity and mortality [59–61].”
IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. (2003, background): “Furthermore, plasma concentrations of IL-6 have been shown to predict total and cardiovascular mortality in population-based studies (25).”