Life Extension Magazine April 2013
How Atherosclerosis Develops in Aging Humans
By William Faloon
At least one of every two Americans over the age of 65 has atherosclerosis.1 It is so common in older people that some experts used to think that it was part of the normal aging process.2
We are going to explain in detail here how atherosclerosis develops, so you can fully understand why a modest dose of fish oil alone is not going to reverse this process in those with preexisting vascular disease.
While we understand that some members may find the material in this article overly technical, it is important we publish it so that our many physician members understand the challenges in treating aging humans with significant pre-existing atherosclerosis.
How Atherosclerotic Lesions Develop
Atherosclerosis begins with changes in endothelial cell function that cause white blood cells moving through the blood to stick to the endothelium (inner arterial wall) instead of flowing by normally.
The endothelium then becomes weakened. This allows blood cells and toxic substances circulating in the blood to pass through the endothelium and enter the artery’s sub-endothelial compartment. Lipid or fat-like substances such as LDL and triglycerides in the blood then accumulate in this area.
The lipids that accumulate in the broken endothelium become oxidized, causing the smooth muscle cells to try to “repair” the damaged endothelium. The result of this repair process is smooth muscle cell infiltration into the endothelium causing the formation of the initial atherosclerotic lesion. Depending on an individual’s risk factors—such as poor diet, lack of exercise, smoking, high blood pressure, and the aging process itself—fat accumulation continues and the atherosclerotic process accelerates.
Immune cells called macrophages then invade the damaged arterial area to digest the fat. But smooth muscle cells that have migrated to the area have already changed their nature to scavenge fat. These fat-laden white blood cells and smooth muscle cells are called “foam cells,” and provoke a chronic inflammatory attack by various immune components.
Smooth muscle cells try to curtail the injury to the endothelium by producing collagen, which forms a cap over the injury site. Calcium then accumulates over the injury site to form a material resembling bone. This is why atherosclerosis used to be referred to as “hardening of the arteries.”
This complex array of foam cells, calcification, and lipid accumulation is called an atherosclerotic plaque. The plaque grows, and if it becomes unstable, it is vulnerable to acute rupture that exposes the contents of the plaque to blood. Platelets can then rapidly accumulate around this ruptured plaque, resulting in an acute blockage (or blood clot) on the inner surface of the blood vessel wall. This clot can become very large and occlude the vessel. Even small plaques, if they rupture, can interfere with blood flow and cause an acute heart attack.
Alternatively, atherosclerotic plaques can grow to such a degree as to restrict blood flow severely. When blood flow within an artery is gravely compromised by a large plaque or blood clot, the cells of tissues that depend on blood flow from that artery become damaged or die. Coronary atherosclerosis cuts off the heart’s blood supply by occluding the heart’s arteries, which stops the oxygen supply to the heart, thus causing a heart attack. An ischemic stroke results when atherosclerotic processes cut off the oxygen supply to a portion of the brain.As you can see, therefore, much more is involved in the development of atherosclerosis than just high cholesterol and LDL. We must emphasize, however, that maintaining optimal LDL and cholesterol levels is an important component of an atherosclerosis-prevention program.
Protecting Your Arterial Walls
High blood pressure,3-7 elevated LDL-cholesterol-triglycerides,8-13 low HDL,14-17 smoking,18-20 diabetes,21-25 obesity,26-30 and lack of exercise31-33 contribute to endothelial dysfunction and the subsequent development of atherosclerosis.
Other significant artery-damaging factors are high-normal levels of glucose,34 insulin,35-39 iron,40-43 homocysteine,44-52 and fibrinogen,53-55 and any level of C-reactive protein14,56-62 that is higher than optimal.
Homocysteine can induce the initial atherosclerotic injury to the endothelium, then facilitate the oxidation of the fat and LDL that accumulate beneath the damaged endothelium, and finally contribute to the abnormal accumulation of blood components around the atherosclerotic plaque.
Fibrinogen is a clotting factor that accumulates at the site of the endothelial lesion. Fibrinogen contributes to plaque buildup and can participate in the arterial blockage after an unstable atherosclerotic plaque ruptures.
Glucose at high-normal levels may accelerate the glycation process that causes arterial stiffening, while high-normal fasting glucose and insulin inflicts direct damage to the endothelium. High levels of iron promote oxidation of LDL in the damaged endothelium, while low levels of testosterone (in men) appear to interfere with normal endothelial function.
C-reactive protein is an inflammatory marker and directly damages the endothelium. Chronic inflammation, as evidenced by persistent high levels of C-reactive protein, not only creates initial injuries to the endothelium, but also accelerates the progression of existing atherosclerotic lesions.
In response to a large number of published studies, enlightened people are taking charge of the health of their arteries. They are eating better, exercising regularly, and undergoing regular blood testing to identify the specific drugs, hormones, and dietary supplements they need to reduce their atherosclerotic risk factors.
The emphasis in treating aging humans with pre-existing arterial disease is that all risk factors should be controlled if there is to be an opportunity to reverse the occlusion of vital arteries. When only a few atherogenic factors like elevated LDL are lowered, disease progression is virtually inevitable, albeit at a slower rate.
At least one of every two Americans over the age of 65 has atherosclerosis.1 A number of biochemical factors in the blood can affect the development of atherosclerosis such as elevated LDL cholesterol, low HDL cholesterol, and elevated glucose, homocysteine or fibrinogen to name a few. Atherosclerosis begins with changes in endothelial cell function that cause white blood cells moving through the blood to stick to the endothelium (inner arterial wall) instead of flowing by normally. The endothelium then becomes weakened. This allows blood cells and toxic substances circulating in the blood to pass through the endothelium and enter the artery’s sub-endothelial compartment. Lipid or fat-like substances such as LDL and triglycerides in the blood then accumulate in this area.
Immune cells called macrophages then invade the damaged arterial area to digest the fat. But smooth muscle cells that have migrated to the area have already changed their nature to scavenge fat. These fat-laden white blood cells and smooth muscle cells are called “foam cells,” and provoke a chronic inflammatory attack by various immune components. Smooth muscle cells try to curtail the injury to the endothelium by producing collagen, which forms a cap over the injury site. Calcium then accumulates over the injury site to form a material resembling bone.This complex array of foam cells, calcification, and lipid accumulation is called an atherosclerotic plaque. This plaque can become unstable resulting in an increased risk of rupture and clot formation. Alternatively, the plaque can continue to grow to a size so large that it impedes or completely blocks blood flow. Either path can lead to a potentially life-threatening stroke or heart attack.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
- Available at: http://www.nia.nih.gov/health/publication/aging-hearts-and-arteries-scientific-quest/chapter-4-blood-vessels-and-aging-rest. Accessed December 21, 2012.
- Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209544/. Accessed January 14, 2013.
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