Over the past 40 years, the most successful pharmacologic approach to cardiovascular disease prevention has been the aggressive lowering of LDL cholesterol. Yet, cardiologists and vascular biologists now have hard evidence that inflammation plays an important role not only in the development of blockages in the arterial system but also in the development of heart failure and chronic kidney disease. Inflammation is a normal part of the immune system’s response to some type of internal injury, assisting with the healing process. But when inflammation persists and becomes chronic, it can lead to vessel injury similar to what is experienced when a joint becomes inflamed. The persistent inflammation leads to the accumulation of fatty deposits and inflammatory cells, leading to plaque formation that predisposes to heart attack and stroke. Cholesterol that accumulates in arteries in patients with elevated cholesterol levels can lead to further inflammation in the wall of the blood vessel, further increasing the risk of heart attack and stroke. We know that patients suffering from a wide range of inflammatory conditions, such as psoriatic and rheumatoid arthritis and ulcerative colitis, are at higher risk for cardiovascular disease.
As research brought the link between inflammation in the coronary arteries and the risk of heart attacks into focus, those of us conducting clinical research asked ourselves if we could find a safe medication that reduces inflammation and lowers cardiovascular risk.
The CANTOS trial showed that an approach targeting a reduction of inflammation had a similar impact on reducing cardiovascular events such as heart attack, stroke, and cardiovascular death, as seen with trials focused on seeing the effect of reducing LDL cholesterol levels on cardiovascular events. Trials looking at the effect of colchicine, an anti-inflammatory drug used to treat gout and reduces inflammation, have shown cardiovascular benefit. Still, its use is limited by the frequent occurrence of diarrhea, its interaction with many commonly used drugs, and its restricted use in patients with moderate to severe chronic kidney disease.
How do I know if I have inflammation?
There are a variety of ways to measure inflammation levels. The most common test to measure for inflammation is the high sensitivity C-reactive protein level, commonly referred to as hs-CRP. This is a simple blood test available through most laboratories. A level greater than two mg/L is considered to indicate an elevated level of inflammation. Less commonly used tests measure interleukin-6 levels. Data from clinical trials indicate that about half of patients with atherosclerosis or blockages in the arteries to the heart, brain, or lower extremities have elevated levels of C-reactive protein despite being on intensive statin therapy for LDL reduction. Such patients are significantly more likely to suffer a heart attack or other cardiovascular event than those with low CRP and low LDL.
Can Inerkeukin-6 be a target for treating inflammation?
Interleukin-6 is a compound that plays an essential role in inflammation. This makes it an attractive target to reduce inflammation and determine this effect in various heart diseases, including heart failure and coronary artery disease, and in patients with chronic kidney disease to prevent progression to dialysis. Ziltivekimab, a treatment currently being evaluated in clinical trials medication being evaluated, is a human monoclonal antibody directed against IL-6, thereby reducing inflammation. Ziltivekimab is administered once a month and has been shown to reduce inflammation as measured by high-sensitivity C-reactive protein in patients with chronic kidney disease and inflammation. Thereby, ziltivekimab has the potential to reduce inflammation in patients with heart failure with preserved and mildly reduced ejection fraction (HFpEF and HFmrEF) and consequently may reduce symptoms, as well as long-term morbidity and mortality. The current study aims to demonstrate the efficacy of ziltivekimab in reducing morbidity and mortality in patients with HFmrEF or HFpEF and systemic inflammation in the Hermes clinical trial and patients with coronary artery disease and chronic kidney in the Zeus trial.
How do I know if I have heart failure with preserved or mildly reduced ejection fraction?
Patients with heart failure will complain of symptoms such as shortness of breath with exertion, fatigue with activity, and/or swelling of the ankles and feet. To be sure that heart failure is the cause of these symptoms, we use a blood test called NT-proBNP or BNP and cardiac ultrasound. These exams are widely available.
To learn more about treating Inflammation, please contact the National Heart Institute @ info@natinalheartinstitute.org. You may be a candidate to participate in our clinical trial program, where new and innovative treatment options are available at no charge to those who qualify.