OXIDATION STATUS NOT CHOLESTEROL DRIVES THE PROCESS
If you ever wish to improve your health status and stop the process of heart disease from going any further then you need to understand what Junk Food TV and your doctor are not telling you. In other words if you don’t wish to have another heart attack or be forced into open-heart surgery, then read on my friend. Of primary importance is the oxidation state of the patient-not his or her cholesterol value. The things that cause endothelial damage and oxidation of LDL are often the things that form free radicals inside the body. Under The Toxic Atheroma description (see part 2 from 2 weeks ago) the authors refer to them as irritating agents (IA). They are the true causes of heart disease which are in addition to classic risk factors such as smoking and the numerous emerging risk factors like metabolic syndrome are the overconsumption of sugar and non-fibrous carbohydrate such as the cereal grains, excessive consumption of inflammatory omega 6PUFA, and a proinflammatory life style which promotes insulin resistance, silent inflammation, and oxidative stress. This usually stems from poor lifestyle choices: the standard American diet (SAD) seen in the Industrial Diner, cigarette smoking and lack of exercise. Two factors alone: lack of exercise and the SAD account for much of the damage that contributes to the formation of atherosclerosis.
Atherosclerosis is the process by which these lesions called plaque form in coronary arteries and other arterial regions such as the aorta and carotid arteries. It’s an inflammatory disease meaning that the body’s immune and repair systems are involved. Acute inflammation started the process but the disease itself involves chronic inflammation since the stimulus for injury never goes away. It takes decades to form usually starting in the teenage years or earlier and ripening when the person enters his 6th decade of life. If you are really unlucky like me it can wound or kill you when you are much younger.
As Dr. Tabas mentioned in his lecture at the 2014 Cardiovascular Disease Prevention Symposium, the first step in stopping inflammation caused by a splinter is to remove the splinter. Atherosclerosis is a result of the immune system’s inability to remove the stimulus (the splinter) consisting of dead immune cells and oxidized fats and lipoproteins from blood vessel walls. Preventing the entry and retention of oxidized non-HDL (oxidized LDL and VLDL make up the splinter) from blood vessel walls would help prevent atherosclerosis.
Preventing entry and retention of oxidized particles is what we do best here in this book. Nearly everything I cover is aimed at this event directly or indirectly.
THE INITIAL EVENT
At the blood vessel’s innermost lining, the endothelium, a particular series of events occurs. As you can see in figure 5 there is an evolution of greater endothelial dysfunction and plaque maturation with each decade. It starts with the initial lesion consisting of foam cell accumulation. As this builds up we see the first visible sign of disease with the fatty streak. After about 40 years we eventually get a fully mature atheroma, a fibroatheroma, with the hallmarks of smooth muscle and collagen within the matrix as well as a small degree of calcification. This figure gives you the impression that atherosclerosis is an unstoppable runaway train of disease and decrepitude. Nothing could be further from the truth. I’ll return to that concept later but first let’s examine the competing theories of this devastating disease. The controversy is over how the initial events occur to set it all off. After that we’ll discuss how preventing this disease from forming applies to most first-world diseases since they all share an inflammatory origin.
Figure 5 Progression of an atherosclerotic lesion
THEORIES OF HEART DISEASE
THE DRAINPIPE THEORY (FOLK LORE)
First let me explain what doesn’t happen and isn’t ever going to happen. There is no real, scientific drainpipe theory. Rather this is the mainstream media’s version of atherosclerosis. It’s even championed on high-impact Commercial Sick Care websites. It says that eating saturated fat and cholesterol clogs your arteries directly or the later ad-hoc version that saturated fat and cholesterol causes your “bad” cholesterol-LDL-to rise and this clogs your arteries. This bad cholesterol, which is circulating in your bloodstream, is deposited in your arteries in the same way that grease ends up plugging your drainpipes. Eventually the drainpipe gets narrower blocking the blood supply and causing a heart attack. This is entirely inaccurate. Even the notion that eating cholesterol and saturated fat causes your “bad” LDL cholesterol to rise has been debunked (see Statin Down the Hatch) by Dr Westman of Duke University Medical Center.
As mentioned previously the problem is that plaque is made of many different inflammatory cells like macrophages and monocytes, fibrin, oxidized lipoproteins, oxidized fatty acids and pus-like material. There may be some saturated fat in a plaque where it acts as the cover membrane on the LDL particle. In patients that eat a lot of saturated fat cell membranes will be rich with it but there are no grossly deposited masses of saturated fat or cholesterol within the plaque. Atherosclerosis occurs under the artery’s inner lining of cells not on top of them so the drainpipe analogy is bad. It goes on to state that the more saturated fat and cholesterol you eat the more plugged your arteries become and the worse your heart disease gets. As it keeps coating your inner vessels it finally clogs them up completely and you have a heart attack. This is utter gobbledygook and no researcher or scientist has ever made these claims but somehow this is the idea the popular press wants you to believe. It sells plenty of statin pills for eager consumers who want to stay healthy.
This idea is endemic. Even the enlightened CEO of Life Extension Foundation Bill Faloon recently got it wrong and wrote an article in March of 2013 on the real causes of atherosclerosis and heart attack. Unsuccessfully, he commented that a heart attack finally occurs with progressive lumen narrowing. There was no mention of how a real heart attack occurs: a young plaque rupturing and spewing its thrombogenic contents into the bloodstream.
This notion of how heart disease forms is an urban legend. Hence you hear sayings like these that spring up: “filled with artery clogging cholesterol,” or “cooked in heart clogging lard or butter.” In fact, the Heart Attack Grill with their Single, Double, Triple Bypass burgers, and their stupefying 8,000 calorie, 630 grams of fat Quadruple Bypass burger, have made this mantra a major selling point. Do you know what the worst inflammation promoting part of that sandwich is? I think you would be surprised. It’s not the saturated fat, that may be the only safe part of this meal. The lack of knowledge on what fuels plaque formation and rupture on the part of the doctor and patient is one of many reasons why cardiac patient’s-trapped in the Commercial Sick Care System-always get worse not better. Toss the Drainpipe theory down the drainpipe.
THE DIET-HEART HYPOTHESIS
The second theory I’ll discuss is called the Diet-Heart Hypothesis. It says that a diet high in saturated fat and cholesterol raise “bad” cholesterol and bad cholesterol causes heart disease. Therefore, a low cholesterol, low fat diet is “heart smart.” See my section on statins for a thorough debunking of this theory in Statin Down the Hatch. Saturated fat and cholesterol do not, I repeat, do not cause heart disease. If I wasn’t sure on this point I’d be dead or at least suffered many more cardiac events or strokes but I haven’t for nearly two decades have I? The diet-heart hypothesis was the prevailing theory for many moons in spite of the fact that it was a house of cheap playing cards built on top of quicksand. This is no more true than the drainpipe theory.
Let’s look at what the scientists really think is happening.
THE RESPONSE TO RETENTION HYPOTHESIS (RRH)
In this third theory scientists speculate that just by having high levels of native, unoxidized, LDL you increase your risk for CVD. In other words, all of your body’s LDL is poison which requires lowering to be in good health. The pathogenesis of atherosclerosis is very complicated and the body of scientific information is not complete but what you should realize right away is that there are many different cells of the immune system involved in plaque formation because it is an inflammatory/immune response to blood vessel injury causing blood vessel inflammation. During our entire investigation into the complex pathogenesis of atherosclerosis try to view this process as the body’s attempt to simply repair a damaged inner lining of an artery. As such many of the same cells I mentioned above in the acute inflammatory response will be present along with a few of the new players in chronic inflammation mentioned earlier. Inflammation is how the body heals itself. It only becomes pathologic when injury continuously occurs and the body cannot adequately heal itself. Once it goes chronic it’s a very different animal. There is one consensus of agreement: once LDL cholesterol has found its way into the subendothelial space-the intima-plaque formation follows a well-defined course. Figures 5 and 6 demonstrate the overall picture of atheroma formation. Let’s try Cecil’s Essentials of Medicine for a description of the RRH:
“In the early phases of atherosclerosis, small lipoprotein particles penetrate the vascular endothelium, where they are oxidized and coalesce into aggregates in the intimal layer [just under the endothelium]. This process is accelerated at sites of endothelial injury…caused by hypertension, smoking, or excessive shear forces [these are some of the classic risk factors]. The accumulation of lipid [more accurately lipoprotein-LDL] aggregates stimulates the expression of adhesion molecules [like opening a door]…on endothelial cells allowing them to bind monocytes [floating in the circulation]. The monocytes [squeeze through the endothelial cells into the subendothelial space] ingest the lipoprotein aggregates to become lipid filled monocytes [more accurately called macrophages] or foam cells. These foam cells make up the earliest visible evidence of atherosclerosis, or the fatty streak. Foam cells release pro-inflammatory mediators, perpetuating the inflammatory process with resultant lesion progression. In addition foam cells release enzymes that cause injury to the endothelium. Circulating platelets adhere to the sites of injury and release growth factors, which stimulate the…..proliferation of smooth muscle cells and fibroblasts from the media (forming the fibrofatty lesion and fibrous plaque). As lipids [lipoproteins and oxidized fatty acids] continue to accumulate they undergo necrosis and leave a …lipid pool in the core of the plaque.”[see figure 4 from last blog part 2]
Note that the author starts his presentation after LDL penetrates into the subendothelial space implying that there need not be anything unusual to occur first to the LDL particle (like oxidation). This theory insinuates that your native LDL is the problem. When you have too many of these particles floating around you develop atherosclerosis. We’ll return to this point in a moment. Let’s examine what we do know to be factual. That would be the point where LDL is already under the endothelial layer forming a fatty streak the first visible sign of disease.
Figure 6 Formation of an atheromatous lesion
Fatty streaks appear as early as age 10 in the aortas of American children only to regress and then to reform later. These streaks may be benign, at least when first formed in young children. Later on, when the streaks reappear and start to grow after decades of proinflammatory living, they become full-fledged plaques as the body attempts to contain the rising number of oxidized LDL particles (oxLDL) that continuously invade the subendothelial space. Foam cells and monocytes send out cytokines to stimulate yet more monocytes, fibroblasts and smooth muscle cells to the site to help fight the unending supply of oxLDL. Eventually they create a core of dead cells filled with oxLDL in pools. The plaques that contain these young, precariously unstable, lipid pools are rich in inflammatory material known as the toxic atheroma. Smooth muscle cells and fibroblasts herald the chronic phase. The big problem is that as the inflammatory stimulus continues certain cells within the plaque will secrete enzymes that over time tend to erode the fibrous cap covering the plaque and make it more vulnerable to rupture which can cause a heart attack. The atherosclerotic lesion is bad enough but it would take decades more to narrow down the arterial lumen to eventually compromise blood flow. When this happens we call it small vessel disease and it is a huge cause of vascular dementia in the elderly. It is not however a common cause of heart attack or stroke. Over time a plaque becomes an old (mature) plaque for lack of a better name and slowly calcifies into stability. These stable plaques go on to behave rather nicely.
Stay tuned as we explore the real cause of atherosclerosis in the next blog. Remember if we can arrest this process we simultaneously avoid the risks for many cancers, hypertension, stroke and about 95 other, popular first world diseases including heart failure which by some estimates will affect 1 in 3 adults over age 55 within their lifetimes. That’s precisely what I did using my dietary plan which cuts inflammation down to a nuisance at worst. That’s how powerful blood vessel inflammation is and that’s why you need to know how it forms and how it’s stopped. Later I’ll introduce you to my Super Mediterranean Diet which is specially tuned toward cooling endothelial fire.
Happy holiday to all, and to all a good day.
The Reality Renegade
 The 2014 Cardiovascular Disease Prevention Symposium. Life Extension magazine. July 2014 page 66
 Andrew D Michaels. Coronary Heart Disease. Andreoli and Carpenter’s Cecil Essentials of Medicine. (Philadelphia, PA.: Saunders Elsevier, 2010) 95
 C Reactive Protein Word Press (http://primumn0nn0cere.wordpress.com/2010/03/23/c-reactive-protein/) 12/17/2011