Considerable evidence supports a role for low-grade chronic inflammation in the atherothrombotic process, from plaque initiation to acute plaque rupture preceding myocardial infarction. Publications in 2018 revealed both the promise and challenges of targeting inflammation to treat atherosclerotic cardiovascular disease and highlighted the importance of understanding the mechanistic diversity of inflammatory pathways contributing to atherosclerosis.
Selective neutralization of the cytokine IL-1β reduces cardiovascular disease events, particularly in individuals who achieved the highest reduction in inflammation as measured by high-sensitivity C-reactive protein (hsCRP) levels1.
Low-dose methotrexate does not protect against cardiovascular disease events and, interestingly, also does not reduce IL-1β, IL-6 or hsCRP levels in high-risk patients2.
Studies in mice indicate that a high-cholesterol diet can induce long-term reprogramming of haematopoietic reservoirs or ‘innate immune training’ to set the stage for higher inflammation via a mechanism involving IL-1β (ref.3).
Inflammation remains an important risk factor after levels of LDL cholesterol have been aggressively reduced, as is now possible with PCSK9 inhibitors in combination with other lipid-lowering therapies4.
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K.J.M.’s work is supported by the NIH (grants R35HL135799 and P01HL131478).
The author declares no competing interests.
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Moore, K.J. Targeting inflammation in CVD: advances and challenges. Nat Rev Cardiol 16, 74–75 (2019). https://doi.org/10.1038/s41569-018-0144-3
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