Targeting inflammatory pathways for the treatment of cardiovascular disease

Abstract

This editorial refers to ‘Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis’[†][1], by S. Kaptoge et al ., on page 578 In the 15 years that have passed since C-reactive protein was linked to future cardiovascular events in otherwise healthy individuals,1 no alternative biomarker has proved to be a superior surrogate for vascular inflammation in the prediction of global cardiovascular risk. This observation is re-affirmed in population-based prospective cohort data from the Danish Research Center of Prevention and Health published by Kaptoge and colleagues in this issue of the European Heart Journal .2 In brief, in age- and gender-adjusted analyses, as well as in full multivariate models, basal levels of the ‘upstream’ pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-18, and tumour necrosis factor-α (TNF-α) were all associated with future vascular events in an approximately log-linear manner, as were levels of matrix metalloproteinase-9. However, and also consistent with prior work in this arena, the magnitudes of these effects were smaller than that associated with the ‘downstream’ inflammatory biomarker, C-reactive protein. Furthermore, among those study participants in whom direct comparison could be performed, only two biomarkers—downstream C-reactive protein (hazard ratio 1.69 per 1 SD higher baseline level) and upstream TNF-α (hazard ratio 1.32 per 1 SD higher baseline level)—remained statistically significant predictors of future vascular risk when simultaneously adjusting for the full panel of cytokines and chemokines. The core question raised in the present analysis, however, does not relate to which inflammatory biomarker is best suited for clinical practice. That issue was addressed in a prior comprehensive meta-analysis from the Emerging Risk Factors Collaboration, in which the incremental utility of C-reactive protein for predicting vascular risk was found to be fully comparable in magnitude to that of total and high-density lipoprotein cholesterol.3 Rather, what the present … [1]: #fn-2