Inflammation is a highly complex process that can occur when the immune system needs to attack what it perceives as a threat, or if there is an injury that needs to be repaired. This generally involves swelling due to extra fluid bringing in cellular reinforcements and increased temperature to help kill pathogens. While temporary inflammation can be annoying albeit helpful, chronic inflammation is associated with a number of diseases such as cancer, Alzheimer’s, diabetes, and heart disease. However, a new paper published in Lancet Diabetes and Endocrinology describes a large meta-analysis that found taking anti-inflammatory medications for a prolonged amount of time may also be bad for the heart, raising many questions.
The study was conducted by the Interleukin-1 Genetics Consortium and utilized medical data and genetic analyses from over one million individuals. In particular, the paper sought out variants of the IL1RN gene, which encodes the interleukin-1 family of pro-inflammatory cytokines. It had been suspected that the IL1RN variations inhibited interleukin-1 pathways, therefore resembling the effect of taking the anti-inflammatory anakinra for a long period of time.
“Drugs such as anakinra are licensed for the treatment of inflammatory conditions including rheumatoid arthritis, but we know little about the long-term health consequences of blocking interleukin-1,” senior author John Danesh of the University of Cambridge said in a press release. “Our approach was to use ‘nature’s randomized trial’ to get answers currently beyond the resolution of drug trials. Our genetic analysis suggests, surprisingly, that blocking interleukin-1 over the long-term could increase the risk of cardiovascular diseases.”
They found that individuals with the genetic variations were less likely to develop rheumatoid arthritis, which is understandable as it is an inflammatory disease. The risk of developing other inflammation-associated diseases such as stroke or diabetes were unaffected. However, the risk of heart disease—which is normally attributed to chronic inflammation—was shown to increase for those with the anti-inflammatory genetic variations, which seemed a bit puzzling.
In fact, this decreased inflammatory response was connected to an increased risk for a number of heart-harming factors. These individuals were more likely to have higher levels of LDL (bad) cholesterol, more likely to experience an aortic aneurysm, and 15% more likely to have a heart attack. This is contrary to what they expected to discover, and it is not clear why that is.
“The common view is that inflammation promotes the development of heart disease – we’ve shown that the truth is clearly more complicated,” lead author Daniel Freitag added. “We need to be careful that drugs like anakinra that aim to tackle rheumatoid arthritis by inhibiting interleukin-1 do not have unintended consequences on an individual’s risk of heart disease.”
Moving forward, the researchers will continue to understand the full role of these IL1RN variants and how they play into overall heart health. Additionally, physicians prescribing anakinra over a long period of time are asked to consider this effect and other risk factors when determining the patient’s overall heart health.