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Reframing Heart Disease: The Role of Inflammation
Most people are aware of the traditional risk factors for heart disease, which include high blood pressure, smoking, high cholesterol, and being overweight. However, it has been observed that many individuals who experience a heart attack do not possess any of these risk factors. Research has revealed that conditions such as gout, psoriasis, inflammatory bowel disease, and rheumatoid arthritis are also associated with an increased risk of heart disease. The common thread among these conditions is chronic inflammation.
In fact, some scientists have started to view cardiovascular disease as a chronic inflammatory disease of the arteries. This concept is referred to as the inflammatory hypothesis of atherosclerotic cardiovascular disease (ASCVD). Atherosclerosis, the formation of fatty plaques in the arterial walls, is a characteristic feature of ASCVD. When this occurs in the arteries that supply oxygenated blood to the heart, it is known as coronary artery disease. ASCVD can lead to heart attacks, where there is inadequate blood supply to the heart, and ischemic strokes, where there is insufficient blood flow to the brain. To understand why ASCVD is an inflammatory condition, we must examine its underlying processes.
The initial stage of atherosclerosis development is believed to involve some form of injury to the endothelium, the thin layer of cells lining the arteries. This injury can be caused by high levels of low-density lipoprotein (LDL) cholesterol, commonly referred to as “bad cholesterol.” Smoking, with its toxins, can also irritate the arterial lining and trigger this initial injury. When the endothelial cells are damaged, they release chemical signals that attract white blood cells, a key component of the immune system, to the site of injury. These white blood cells enter the artery wall and initiate inflammation within the artery. Additionally, these cells consume the cholesterol present in the arterial walls, resulting in the formation of “fatty streaks” – visible signs of early-stage atherosclerosis. Fatty streaks can begin to develop at a young age, and by the time we reach our twenties, most of us will have evidence of these streaks in our arteries. This process of endothelial cell damage, white blood cell infiltration, and chronic inflammation can continue silently over the years, eventually causing plaque buildup in the arteries. This may explain why individuals with chronic inflammatory conditions are at an elevated risk of cardiovascular disease. Prolonged inflammation in the arteries supplying the heart and brain can ultimately give rise to heart attacks and strokes.
A heart attack occurs when a plaque in the artery supplying the heart becomes unstable. This instability can lead to rupture, resulting in the formation of a clot within the artery and interrupting the blood supply to the heart muscle. Patients who experience a heart attack often exhibit higher levels of inflammation and plaque instability in the days and weeks preceding the event. The eventual occurrence of a “heart attack” and the subsequent damage to the heart muscle can be seen as the culmination of this unstable inflammatory process. In a groundbreaking clinical trial named Cantos, researchers tested the inflammatory hypothesis of cardiovascular disease by treating heart attack patients with high levels of high-sensitivity c-reactive protein (hs-CRP) with an anti-inflammatory drug called canakinumab.
Fortunately, there exists a method for measuring inflammation in the body through a blood test known as hs-CRP. Elevated levels of hs-CRP are linked to an increased risk of heart attacks and strokes. Higher levels of LDL cholesterol also serve as a risk factor for ASCVD. Multiple studies have reported that individuals with high levels of both LDL cholesterol and hs-CRP are at the greatest risk of cardiovascular disease. The Cantos trial demonstrated the potential of targeting inflammation in reducing the risk of recurrent cardiovascular events. Treatment with the anti-inflammatory drug, canakinumab, resulted in reduced levels of hs-CRP and a statistically significant decrease in the number of heart attacks experienced by the patients. However, the increased risk of infections associated with the drug and its high cost make its widespread use in ASCVD treatment unlikely at present. Nevertheless, the study provided significant support for the hypothesis that inflammation plays a pivotal role in ASCVD and highlighted the potential of targeting inflammation to mitigate cardiovascular risk.
Accepting this paradigm shift in understanding ASCVD risk factors may enable us to better identify individuals at risk of heart attacks and strokes. It may also facilitate the development of strategies for treating inflammation to reduce cardiovascular risk. Several studies are currently investigating the use of more affordable anti-inflammatory drugs, such as colchicine and methotrexate, to decrease inflammation and impede the progression of cardiovascular disease.
Fortunately, it is possible to reduce inflammation in our bodies without resorting to medications. We can categorize our lifestyle choices as either pro-inflammatory or anti-inflammatory. Smoking, with its toxins, promotes inflammation in the body. High levels of cholesterol in the blood and a diet rich in ultra-processed foods can also lead to chronic inflammation in our arteries. Conversely, an anti-inflammatory diet, characterized by a high intake of fruits, vegetables, whole grains, and fatty fish, is deemed beneficial. Exercise has also been found to lower inflammation levels in the body. Chronic inflammation is linked to obesity, especially when excess weight is concentrated around the midsection. Therefore, losing weight around the midsection can help mitigate inflammation. Stress also triggers a chronic, low-grade inflammatory response in the body, emphasizing the importance of stress management. Maintaining healthy blood pressure, cholesterol levels, and body mass index, the traditional markers of heart disease risk, is equally significant. By making anti-inflammatory choices and adopting a healthy lifestyle, we can all reduce our chances of developing heart disease and enhance our overall quality of life.
