The Patient Was…

Inflammation and Coronary Heart Disease are two well-known medical phenomena that play significant roles in human illness. Each has been recognized and, in large measure, understood from its symptoms and consequences.

The symptoms and signs of acute inflammation include, most notably, pain, swelling, redness, and heat in the area involved. These usually represent the body’s normal response to injury or infection. Physiologically, the immune system is activated and produces certain enzymes and chemicals and sends specialized cells to the affected area. Acute inflammation is generally considered a defense mechanism to combat a “noxious” stimulus of some sort. But inflammation can be a chronic process, as well, and here its role and sequelae are much less understood.

Coronary heart disease (also commonly known as coronary artery disease and ischemic heart disease), the cause of most heart attacks, is well known worldwide. Heart disease is the leading cause of mortality in the U. S., causing almost one million deaths annually, about one third of which are due to coronary heart disease. The classic concept of coronary disease is as an “atherosclerotic” disease (atherosclerosis: hardening of the arteries), where cholesterol-laden plaques build up in the walls of the arteries supplying the heart muscle and block the blood flow.

Although the two processes, inflammation and coronary heart disease, have been known for many decades, it is only in recent years that they have been recognized as closely linked. The interrelationships of chronic inflammation and coronary heart disease have led not only to new understandings of the development of coronary artery disease, but also to new diagnostic and therapeutic strategies for treating and managing it.

An article in recent years, in the International Journal of Molecular Sciences, describes atherosclerosis as a “chronic inflammatory disease, in which the immune system has a prominent role in its development and progression.” The mechanisms by which inflammation and plaque development in arteries interact are very complex and are the subject of much research.

Some years ago, when I was serving as Medical Director for a major pharmaceutical company interested in both heart disease and inflammation, I surveyed five of the leading cardiologists in the country about where they thought the future of cardiology research and patient care were heading, and which areas of inquiry would lead to the most fruitful outcomes. Although each had different ideas, they all agreed that inflammation would be a key element. What was unclear then, and is still not fully resolved, is how the very complex processes of inflammation interact with the equally complicated mechanisms of atherosclerosis and plaque formation.

In general, and in very simplified terms, it seems that inflammation of the inner lining of the blood vessels allows fatty substances, especially molecules of cholesterol and other lipids (fats), to penetrate into the deeper layers of the artery wall. Different types of pro-inflammatory cells then accumulate in the area and produce enzymes and chemicals that further the inflammatory process. A cap forms over the plaque and, depending on the degree of inflammation, the cap may weaken and break. This, in turn, sets in motion a process of clot formation that blocks the blood flow in the artery and causes heart attacks and other damage.

What has only recently become apparent is that to fully address the problems of coronary heart disease, inflammation as well as cholesterol and other blood lipids must be addressed. Even with normal levels of cholesterol and other lipids in the blood, the processes of inflammation can drive coronary artery disease. Elegant studies have shown that when inflammation is active, even with good levels of cholesterol, artery damage can proceed and lead to rupture of plaques in the blood vessel walls, with resulting heart attacks.

One of the unsettled problems is how best to reduce the inflammatory processes occurring within the blood vessels. Common anti-inflammatory drugs, used to reduce more acute inflammation, do not seem to work well in this regard and, in fact, may be damaging to the body in other ways.  There are numerous pro-inflammatory substances released by cells that play active roles in internal inflammation. Which ones are most important in the process of atherosclerosis is still a subject of research. And while there are also natural anti-inflammatory molecules released internally, attempts to identify and manipulate them to reduce vascular inflammation is still experimental.

Interesting and more clinical research has recently tested the effects of older medications, commonly used to treat different types of inflammation, in patients with heart disease. Colchicine, for example, an inexpensive, long-used drug to treat the inflammation in gout, has been shown to reduce inflammation in some patients with heart disease, leading to a reduction in bad cardiac outcomes.

There is now a validated test for inflammation, called hsCRP (high sensitivity C-Reactive Protein), that has largely replaced an older, less sensitive one called ESR (Erythrocyte Sedimentation Rate). It is reported that an elevated hsCRP level in the blood can predict coronary heart disease years before other manifestations. While many forms and causes of inflammation can increase the level of hsCRP, finding an elevated value should at least prompt a look for the cause. In patients with known or suspected coronary disease, elevation of the blood hsCRP level may be the impetus for more aggressive therapeutic action.

There is, as stated earlier, no specific treatment for the inflammation associated with coronary artery disease. But if hsCRP is used as a guide, a treatment that reduces the level of this indicator of inflammation without untoward side effects is likely to be beneficial. It is notable, in this context, that statin drugs, which are perhaps the bulwark against atherosclerosis, can lower hsCRP levels. It is believed by many experts that some of the benefits of statins in patients with coronary disease are due to their anti-inflammatory properties and not just their effects on lowering levels of cholesterol.

Lest you think that much of this link between inflammation and heart disease is still theoretical and in the research phase, a striking example of its practical significance relates to immunization for various infectious illnesses, including flu (influenza) and COVID. These infections, like others, produce an inflammatory response within the body, and there is excess cardiovascular mortality during influenza epidemics.  Influenza, pneumonia, and several other infections not only increase the risk of developing a heart attack in the immediate post-infection period, but this increased risk can persist for months and even years. Years ago, it was shown that flu shots (seasonal vaccination against the flu) reduced the likelihood of heart attacks for almost the entire year following vaccination. And more recently, similar studies on vaccination against COVID have shown similar reductions in cardiac disease during the months following vaccination.

Remember, acute inflammation is often recognized by its traditional accompaniments: pain, redness, swelling, heat. Chronic inflammation, on the other hand, may be silent or may manifest in ways not traditionally associated with signs or effects of an inflammatory reaction. But chronic inflammation may play an important internal role in advancing atherosclerotic vascular disease. Understanding and addressing this may prove to be a most important part of treating and managing heart disease.