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Interleukin-6 (IL-6) is a cytokine centrally involved in several immunological processes and has been recognized as a driver of enhanced atherothrombotic risk. Immunity and inflammation are intrinsically involved in atherosclerosis progression. This generated ‘inflammation hypothesis’, which is now validated in large-scale clinical trials. Abundant evidence supports the distinctive role of IL-6 in coronary artery disease. The focus on this cytokine stems from epidemiological studies linking high plasma concentrations of IL-6 with greater risk for adverse cardiovascular events, genetic studies which implicate a causative role of IL-6 in atherosclerosis and murine data which support the involvement of IL-6 in various pathophysiological cascades of atherothrombosis. The fact that high IL-6 levels are equivalent to the increased cardiovascular risk created an unmet need to address those who are at ‘residual inflammatory risk’. Moreover, the opposing effects of IL-6 underlined the importance of deciphering the individual signaling cascades, which may be responsible for different effects. Finally, murine data and some small clinical trials highlighted the possibility of reversing the pro-atherogenic effects of IL-6 by directly targeting it. While IL-1 blockage proved effective, it is reasonable to examine if moving more downstream in the inflammation cascade could be more selective and effective than other anti-inflammatory therapies. In the present review, we examine the role of IL-6 as a biomarker of ‘residual inflammatory risk’, its vital role in the pathophysiology of atherosclerosis progression and the possibility of targeting it to stall coronary artery disease progression.

Oxidative stress plays a central role in atherogenesis, implicated in endothelial dysfunction, coronary plaque formation, and destabilization. Therefore, identifying oxidative stress in the vascular wall by reliable biomarkers could aid in early diagnosis and better coronary artery disease (CAD) prognostication. Because of the short half-life of reactive oxygen species, the current approach is to measure stable products generated by the oxidation of macromolecules in plasma or urine. Most popular oxidative stress biomarkers are oxidized low-density lipoprotein, myeloperoxidase and lipid peroxidation biomarkers, such as malondialdehyde and F2-isoprostanes. Oxidative protein modification biomarkers and oxidized phospholipids have also been studied and discussed in the present review. Most of these biomarkers are associated with the presence and extent of CAD, are elevated in patients with acute coronary syndromes, and may predict outcomes independent of traditional CAD risk factors. However, further standardization of measurement methods and assessment in large randomized clinical trials are required to integrate these biomarkers into clinical practice. In addition, evidence that these biomarkers detect oxidative stress in the vascular wall lacks and more specific biomarkers should be developed to identify vascular oxidative stress. Consequently, several oxidative stress biomarkers have been developed, most of which can be associated with the presence and extent of CAD and event prognosis. However, they still have significant limitations that hinder their integration into clinical practice.