But what exactly is heart disease? When we think of heart disease the first thing that comes to mind is arteries clogged full of cholesterol rich plaque deposits, right? While that is true, it doesn’t convey the true picture. For over half a century we have been led to believe that heart disease is a disease of over-consumption of fats, especially saturated animal fats – and that it’s mainly a disease of cholesterol overload. So in recent decades we have been cutting down on all fats and have reduced our dietary cholesterol consumption at an unprecedented rate. Yet heart disease has grown from a rare disease in the early 1900s to the number one killer today. Something doesn’t add up, does it?

Cholesterol is a vital substance that plays an important role in our body. It protects the cells from dying. It is the substance from which all sex hormones (testosterone, estrogen etc.) are made. It also helps the liver produce bile that aids in digestion. Without cholesterol our cells would die easily and need frequent regeneration. Our brain and Central Nervous System (CNS) use the greatest amount of cholesterol, as they don’t regenerate like other cells found around our body. This is why according to Dr. Aseem Malhotra, a London based cardiologist, 20% of the people on statin drugs (like Lipitor and Crestor) to lower cholesterol suffer unwanted side effects like memory loss, and other neurological symptoms of depression and dementia.

Although cholesterol is found in plaque, it’s not the cause but rather a consequence of another localized “phenomenon,” which drives it to form plaques in certain areas of the arteries and that localized “phenomenon” is free radical damage and inflammation.

First let’s understand the role of free radicals in our body. Free radicals are byproducts of various metabolic processes that happen inside normal cells. Free radicals can also come from external sources like diets rich in processed foods, environmental toxins and pollutants, smoking etc. These are highly reactive (and unstable) molecules that attack (or oxidize) other healthy cells and turn them into free radicals. They are sort of like rogue thieves that rob other healthy cells and turn them into thieves as well. These newly made thieves then attack other healthy cells and make new thieves and so on and so forth. You can see how this sets a chain reaction making new free radicals along the way.

The natural question then is how does free radical damage cause plaque formation? The detailed description belongs in the biochemistry textbooks, but here is a simple description: In a normal, healthy artery, the innermost layer of artery is covered by a thin lining of (endothelial) cells. This lining acts as a filter for transporting material (like white blood cells) in and out of the bloodstream. The endothelial lining is also responsible for controlling the blood pressure by relaxing and contracting the artery. At any given instance, tiny particles of cholesterol (also known as LDL or “bad” cholesterol) slowly move in and out of the endothelial lining. So far so good. The problem comes when these LDL particles get oxidized due to free radical attack. These altered and oxidized LDL particles then start coalescing (sticking) to form large drops of ox-LDL particles (normal LDL resists this stickiness).

This is where the second piece of the puzzle, inflammation, comes into play. Broadly speaking inflammation is the body’s immune system response to something that might turn out to be harmful. So, as these coalesced ox-LDL particles reach larger sizes they start an inflammatory response in the endothelium in order to clean up and scavenge these damaged particles. White blood cells (monocytes and lymphocytes) which are primarily meant for inflammatory response get called in to clean up these globs of ox-LDL particles. Just as a vacuum cleaner sucks up dirt and debris these monocytes start gobbling up large quantities of ox-LDL particles. As these monocytes grow larger they develop receptors (sticky sites) that attract more altered and oxidized proteins and lipids found in the tissue. At this point the monocytes become macrophages that are the most important cleanup cells found in tissues.

Over a period of time the cholesterol-rich core in the macrophages keeps expanding to form a plaque, which develops a fibrous cap on top, just as a scab develops when we scrape our knee on the pavement. Over time, this fibrous protective cap starts eroding from underneath as the cholesterol deposits continue, and as more and more free radical damage occurs around it. Eventually the fibrous cap becomes unstable, ruptures and falls off, ripping the endothelial lining in the process. This causes a rapid clot formation at the site of rupture. A large enough clot will completely block off the flow of blood in the artery. This phenomenon of plaque formation and progression is shown in figure 1.

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(Above): Figure 1. Schematic representation of plaque formation over time.

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When such a ruptured plaque blockage happens in an artery that supplies blood to the heart the person suffers a heart attack which results in permanent heart damage and quite possibly death (figure 2 left). When this happens in an artery supplying blood to the brain an Ischemic stroke can occur causing permanent brain damage (leading to paralysis) or death (figure 2 right).

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(Above): Figure 2. Schematic representation of heart attack vs. ischemic stroke (Courtesy of National Institutes of Health at www.nih.gov)

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We can see how free radical attack in the endothelial lining initiates the formation of plaque and how the resulting inflammation facilitates its growth. In fact inflammation plays such a crucial role in the formation of plaque that markers of inflammation in the blood, also known as C-Reactive Proteins (CRP) are better predictors of heart disease than total or LDL cholesterol levels.

Free radical damage has furthermore been implicated in several degenerative diseases like rheumatoid arthritis, cerebrovascular disease, Alzheimer’s, Parkinson’s, pulmonary disease, macular degeneration and cancer. In fact the free radical theory of aging proposes that our cells deteriorate (age) as a result of free radical damage over time. For example, collagen exposed to free radical attack (from say UV exposure) loses its elasticity, causing the formation of wrinkles in the skin.

Usually our body is capable of neutralizing the free radicals that are generated during the process of normal cell metabolism, but in recent times the assault of processed foods loaded with unnatural trans-fats and chemicals and the presence of environmental toxins and pollutants has risen dramatically especially in the developed world and so has heart disease. Stress, obesity and smoking are three other leading causes of free radical damage to our body. Together the collective assault of stress, obesity and free radical damage is giving our heart a lot of grief, and in order to mitigate this we need to control and minimize all of them.  Eating plenty of antioxidants to neutralize the free radicals, managing our insulin levels to keep our weight under control and worrying less will ensure our heart keeps ticking for a long time.