Today marks the beginning of a series of articles on inflammation. Why not right? After all my upcoming book is titled InflaNATION: The Industrial Diner and a Doc in the Box. You may have guessed correctly based on the title that I have a few things that I need to get off my chest, (like plaque quite literally). Inflammation is the single most important concept in this book and in all of preventive medicine. If it is not the root cause of our diseases of affluence, it plays a major role in their making. It demonstrates how widely differing diseases share a common origin. In America and other industrialized countries we currently suffer from an epidemic of blood vessel inflammation which has spawned our nation’s first killers: heart disease and stroke. Once you know and understand how inflammation generates disease you will realize how important it is to change the way you currently live if it is generating inflammation. This explains why changing one’s diet and lifestyle to an anti-inflammatory approach helps to prevent or sometimes cure many different, seemingly unrelated diseases. That is why you need to read and understand what inflammation is, what it does, and how we can stop it. Our very lives depend on this knowledge. Unfortunately, the modern American lifestyle: the way we eat, drink and be merry is now costing us dearly. We are now a nation of the sick and inflamed we are the InflaNATION.
Chronic inflammation is closely associated with cardiovascular disease (CVD), as well as a broad spectrum of neurodegenerative diseases including Alzheimer’s disease (AD). It turns out that inflammation is at the center of many diseases we see in the western world. In perhaps one of the most profound revelations in medicine, it turns out that nearly all of the diseases from which modern Industrial people suffer from have an inflammatory origin or component. The implications are staggering. It means that our lifestyle is “broiling” our organs slowly over time putting us straight on the path toward one of the major killers in this country. This also means that any strategy that decreases inflammation from let’s say the coronary arteries will also help to decrease inflammation in any other organ system like the brain. Therefore, when I set out years ago to “cure” my heart disease I also massively decreased my chances for neurodegeneration, cancer and autoimmunity too. I didn’t even have to try-it came with the turf so to speak. That’s exceptional news when you think about it because it tells us that there is one relatively simple path to take which liberates us from the top killer diseases of the first world. There are inflammatory mechanisms in stroke, CVD, diabetes, cancer, obesity, many chronic autoimmune processes and perhaps some psychiatric disorders like depression to name just a few. As you can see from this small example we are talking about the major diseases of western civilization: the so called diseases of affluence. We need to eliminate the sources of inflammation at their origins but first let’s examine what inflammation really is.
WHAT IS CHRONIC INFLAMMATION
I’ll start with chronic inflammation since this is the type or response that we are trying desperately to decrease or eliminate. It is an unchecked biological reaction to tissue injury producing a smoldering, cascade of immuno-vascular responses in an attempt to heal, leading to a pathologic change in the cell population of the affected tissue. It is characterized by repeated healing and injury.
Whoa say what? Yes, my pixilated parrot, chronic inflammation is a never ending immune response to our bad lifestyle and eating habits. It is real tissue injury. In this case we are referring to atherosclerosis which I’ll define for you below.
Acute inflammation is a “first response.” It is not intended to drag on for week after week. It is a protective response anticipated to eliminate the initial cause of cell injury, remove the damaged tissue, and generate new tissue. When the stimulus remains for over 2-4 weeks the tissue response goes chronic.
So inflammation is a tissue response to injury involving several different cell types of the immune system, the clotting cascade and other special plasma proteins. It can occur anywhere in the body. Let’s have a look at one special type of chronic inflammation since it is the most prevalent in American society. At the cellular level we have a typical arterial blood vessel as shown in figure 1 below.
The vessel has three layers, the outermost the tunica adventitia followed by the muscular tunica media and the innermost layer the tunica intima. The inner most layer of cells lining the tunica intima is the endothelium a monolayer of specialized cells. This is the area that concerns us since heart disease starts in the endothelium and progresses into the intima, or subendothelium technically. This is where plaque forms.
Figure 1 Cross section of a blood vessel
A BRIEF HISTORY OF ENDOTHELIAL INFLAMMATION
The endothelium is a very active layer of cells and comprises the largest endocrine system in the body. Inflammation can manifest anywhere but when it occurs right under the endothelium we have the beginnings of cardio “vascular” disease. But first something needs to happen to sicken the endothelial cells. If this doesn’t occur you cannot develop heart disease. Most commonly these are the traditional “risk factors” for heart disease like smoking or a first degree relative with heart disease. But there are others such as the lifestyle choices people make like not exercising or eating sugary foods instead of a salad for lunch. Once the endothelium sickens it can no longer maintain its proper role as an endocrine organ in blood vessel health. It’s a state called endothelial dysfunction. It is this dysfunction that is at the heart of heart disease. It’s the most fundamental process of all leading directly to CVD. If this process continues unabated, eventually foam cells form under the endothelium followed by a fatty streak, the first indication of plaque visible to the naked eye, followed by an atheroma which we all know by the term plaque. This plaque is the result of an inflammatory immune response that has gone chronic. Usually it takes many decades for this to develop and lead to arterial plaque buildup. Should it rupture, it often leads to a heart attack or stroke. Let’s return to this a little later. I want to cover the acute response in greater detail because it is vital for human health and need not be confused with the chronic response. We need some inflammation to be healthy.
THE CLASSIC ACUTE INFLAMMATORY RESPONSE
The classic inflammatory response was first described by the Aulus Cornelius Celsus (c. 25 B.C.-c. 50) in De Medicina. De Medicina‘s contents came from a vast collection of writings of the school of Hippocrates. In fact, in De Medicina, Celsus (although apparently not a physician himself) references some 80 Greek medical writers and he has been called both the Roman Hippocrates and the Cicero of Medicine. His medical philosophy was also influenced by Asclepiades, who established Greek medicine in Rome, and by the famous medical school of Alexandria. He characterized the five cardinal signs as Dolor (pain), rubor (redness), calor (heat), tumor (swelling) and Functio laesa (loss of function). This classic response is what you see when you puncture your skin with a thorn for example. Another example would be an infected joint where we see a painful, swollen, warm, red joint with decreased function.
When silent inflammation becomes overt inflammation we often experience pain along with the other four cardinal signs listed above. Pain then is our warning sign that something is wrong. But pain is not experienced in the blood vessel even with steady, smoldering, inflammation because there are no nerve endings in the endothelium. Other areas can be the same where we have plenty of chronic low-level inflammation without any warning signs of overt discomfort. Often times a threshold needs to be reached before the patient will experience pain from sometimes profound levels of silent inflammation.
Inside the blood vessel all of the classic things are happening but in a way that we cannot tell without sophisticated tests. In other words it doesn’t hurt. You have no idea that it’s occurring-until perhaps, one day, you have a heart attack. That’s why it’s called silent inflammation and that is why it is so deadly!
WHAT IS PLAQUE?
Figure 2 Atheroma within blood vessel
We hear plenty on TV about plaque and cholesterol as if the two were the same but are they? In simple terms a plaque is a collection of dead white blood cells and other immune cells along with oxidized lipoproteins (oxLDL) and oxidized fatty acids making up a pool of gruel with a necrotic core covered by a thin cap not unlike a whitehead pimple (figure 2). Notice how I did not say it was filled with cholesterol but rather lipoproteins, fatty acids and pus? Besides pus the most commonly found substance in your average American’s plaque is not cholesterol but rather oxidized fatty acids: about 75% of which are omega 6 fatty acids, the heart smart fats. This should be one of those “duh” moments where you suddenly realize that the American Heart Association’s advice to eat plenty of omega 6 polyunsaturated oils may not be the best advice. Here, sitting right in your plaque burden is that oil your doctor told you to eat more of, and it’s already oxidized. That’s not good.
Two types of plaque form in a patient with atherosclerosis. They are characterized as young and unstable or older, more stable plaques. In younger plaques this inflammation, characterized by repeated healing and injury, can become very dangerous.
It is the younger plaques that are of concern. They tend to have a very thin covering or cap protecting the immuno-lipid pool from entering the blood stream. Unchecked inflammation weakens this cap further still. If the patient continues to live a typical American lifestyle eating pro-inflammatory foods; maintaining deficiencies in micronutrients and vitamins; remaining sedentary and overweight; we might see the patient develop unstable angina or a heart attack when the plaque finally ruptures and spills its atheromatous gruel into the bloodstream.
This gruel is highly thrombogenic, that is, it activates platelets to instantly stick together and initiate a deadly blood clot as seen in figure 3. Should this plaque rupture occur within a coronary vessel a blood clot forms which often leads to a heart attack. This is what I experienced. The excitement and catecholamine release from the events of Christmas cooking, along with the highly pro-inflammatory state I was in: overweight, work stress, no sleep, fast food and no exercise, was enough to cause it. If this were to occur in a brain blood vessel it would lead to a stroke with devastating consequences. From scientific investigation we know that inflammation is present from the very beginning of cardiovascular disease.
…inflammation contributes across the spectrum of cardiovascular disease, including the earliest steps in atherogenesis. This recognition has had a profound impact on our understanding of atherothrombosis [blood clot] as more than a disease of lipid accumulation, but rather as a disorder characterized by low-grade vascular inflammation. Practically, we can use this concept to predict future cardiovascular risk. [Emphasis mine]
Figure 3 Hemostasis: formation of a platelet plug and initiation of the coagulation cascade
In my next posting (in 2 weeks) I’ll continue our discussion on inflammation, the most important concept in all of preventive medicine.
Paula Grammas. Neurovascular dysfunction, inflammation and endothelial activation: Implications for the pathogenesis of Alzheimer’s disease Journal of Neuroinflammation. (http://www.jneuroinflammation.com/content/8/1/26) 12/12/2011
 Carol Mattson Porth, Glenn Matfin. Pathophysiology Concepts of altered Health States. (China, Wolters Klewer Health/Lippincott Williams and Wilkins 8th Ed. 2009), 377.
 Chris Masterjohn Cholesterol-and-health.com 12/08/2011.
 Dr Rajan Bowri http://heart-diabetes.blogspot.com/ http://upload.wikimedia.org/wikipedia/commons/c/c2/Atherosclerosis_diagram.gif
 Balylock Wellness Report. May 2013 p. 5
 Peter Libby, Paul M. Ridker and Attilio Maseri. Inflammation and Atherosclerosis. Circulation 2002, 105:1135-1143