Cholesterol Part 4: The Role of Inflammation
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Introduction | Inflammation | Where does it Come From? | C-Reactive Protein | Homocysteine | What to Do | References |


You’ve learned that fat doesn’t necessarily make you fat. You’ve learned that cholesterol in your diet does not necessarily lead to atherosclerosis. You’ve learned that the commonly prescribed medications to lower cholesterol can have extreme side effects for the muscles and the brain due to their disruption of production of CoQ10. You’ve learned that if your cholesterol goes too low, you have increased risk for depression, anxiety, violent behavior, and suicide due to depletion of dopamine and serotonin which require cholesterol for production.

So, if cholesterol and fat in our diets are not the culprits, where does this leave us in the “war” on heart disease?

There are many other factors in the development of cardiovascular disease, and the one receiving the most attention from the scientific community these days is inflammation.  back to top


flamesIn the world of Chinese medicine, most things boil down to a balance between yin and yang. If there is too much yin there are problems. If there is too much yang there are problems. When there is balance, there is relative health. Yin is thick, sticky, dark, and cooling. Yang is hot, bright, and rapidly moving. A good analogy is night and day.

When you sprain an ankle, it becomes hot, swollen, and painful. Onset of symptoms is rapid. This is a yang condition. Typical treatments include anti-inflammatory medication, ice, and rest, all “yin” treatments. The ankle sprain is an acute condition with rapid onset and a clear recovery path. Inflammation can also come on more slowly, sort of like the story of the frog in a pot of water that starts out enjoying the warmth until it realizes it is being cooked. Regardless of the speed of onset, inflammation is a yang condition, and it requires something yin to restore balance.

Inflammation in the arteries has been consistently noted in autopsy reports of patients with atherosclerosis. As artery walls become inflamed, the vessel walls lose their integrity and begin to leak. Cholesterol molecules plug the leaks in the artery walls. Some types of cholesterol are sticky, and cause other cholesterol molecules to attach to them. Over time, the yin response of cholesterol production leads to bigger and bigger buildups of fatty plaques in the artery walls, what we know as atherosclerosis. As the fatty plaques build up, the arteries become less resilient. When the vessels are less resilient, blood pressure increases. Less resilient arteries are more likely to tear when under pressure, leading to increased likeliness of heart attack or stroke. Inflammation leads to leaky arteries, plaque build-up, decreased artery wall resilience, and increased likelihood of artery tearing. Cholesterol is one of our body’s mechanisms to try to dampen this inflammation and stop the leaks. As the cholesterol level in our bloodstreams increases, it is an indication that our arteries are becoming more and more inflamed. back to top

So where does inflammation come from?

One of the most common underlying causes of inflammation is stress. Whether physical or emotional, stress leads to a series of changes in our nervous systems and immune systems which lead to inflammation. Every time your child drives you crazy, you find yourself screaming at another driver, your boss squashes your enthusiasm for a project, or your parents make you feel like a naughty five year old, your body produces cortisol which activates a cascade of chemical changes in your body. Over time, these changes can lead to inflammation.

man_eating_fast_foodIf you have food sensitivities, every time you eat that piece of pizza or drink that milk shake, the offending food irritates the lining of your intestines.  Over time, this irritation leads the intestine walls to leak and your body begins to dump chemical irritants into the blood stream rather than excreting them. These irritants create inflammation in the nervous system and the blood vessels as well as the intestines.

For an extreme example, think about how your skin reacts when you come in contact with poison oak. Now, imagine an allergic reaction with red, swollen, lumpy, oozing irritation in your intestines and blood vessels after coming in contact with a food your body reacts to.

Inflammation can also be the result of a virus, bacteria, fungal infection, or parasite. You have experienced what happens when your nasal passages become inflamed and swollen when you have a cold. Some pathogens in the blood stream can cause similar inflammation in the arteries. Inflammation can cause an immune system reaction, and inflammation can be caused by an immune system reaction.

In the 1980s, according to Dr. Klaus Ley, immunology researchers first found that plaque buildup in the arteries also contained inflammation-causing T cells of the immune system. "This opened up the possibility that the inflammatory process was important in heart disease," said Dr. Ley. Further study found that inflammatory T cells not only contributed to plaque formation, but they also played a key role in the rupture of the artery wall, which produces a heart attack. (15)

How do we measure inflammation, and how does this impact on heart disease? There are several inflammatory markers which are easily tested with a blood test. None is a perfect indicator for heart disease risk, but each provides a piece of the puzzle which brings us closer to estimating an individual’s risk. back to top

C-Reactive Protein

The most common measure, which is being tested more and more frequently in main-stream medicine, is C-reactive Protein (CRP). CRP levels rise dramatically when inflammatory processes occur in the body. This increase is due to a rise in the blood concentration of Interleukin-6, which is produced predominantly by white blood cells and fat cells. It is also believed to play another important role in innate immunity, as an early defense system against infections. (13, 26)
CRP rises up to 50,000-fold in acute inflammation, such as infection. It rises above normal limits within 6 hours, and peaks at 48 hours. Its level is mainly determined by the rate of production (and hence the severity of the precipitating cause).

A high-sensitivity CRP (hs-CRP) test measures low levels of CRP using laser technology. The test gives results in 25 minutes with a high sensitivity. Normal concentration in healthy human blood is usually lower than 10 mg/L, slightly increasing with ageing. Higher levels are found in late pregnant women, mild inflammation and viral infections (10–40 mg/L), active inflammation, bacterial infection (40–200 mg/L), severe bacterial infections and burns (>200 mg/L). (13)

A growing number of studies have examined whether hs-CRP can predict recurrent cardiovascular disease, stroke and death in different settings. High levels of hs-CRP consistently predict recurrent coronary events in patients with unstable angina and acute myocardial infarction (heart attack). Higher hs-CRP levels also are associated with lower survival rates in these patients. Many studies have suggested that after adjusting for other prognostic factors, hs-CRP is useful as a risk predictor.

heart_attackScientific studies have found that the higher the hs-CRP levels, the higher the risk of having a heart attack. In fact, the risk for heart attack in people in the upper third of hs-CRP levels has been determined to be twice that of those whose hs-CRP level is in the lower third. These prospective studies include men, women and the elderly. Studies have also found an association between sudden cardiac death, peripheral arterial disease and hs-CRP. However not all of the established cardiovascular risk factors were controlled for when the association was examined. The true independent association between hs-CRP and new cardiovascular events hasn’t yet been established.

In addition, there is research that indicates an infection — possibly one caused by a bacteria or a virus — might contribute to or even cause atherosclerosis. The infectious bacteria, chlamydia pneumoniae, has been shown to have a significant association to atherosclerotic plaque. The herpes simplex virus has also been proposed as an initial inflammatory infectious agent in atherosclerosis. (1)

The link between elevated CRP levels and heart disease has been demonstrated repeatedly, and there is some evidence that CRP may be a more important indicator of heart disease risk than high LDL ("bad") cholesterol. In an eight-year study involving 27,939 women led by Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital in Boston, more than half of the women who eventually developed heart disease had high CRP levels even though their LDL levels were not considered high. Dr. Ridker has estimated that the same may be true for 25 percent of the U.S. population. The study results were published in the November 14, 2002, issue of the New England Journal of Medicine. More recently, a Cleveland Clinic study found ultrasound evidence that clogged coronary arteries had not gotten worse among 502 patients who were most successful at lowering their CRP levels. The study was published in the Jan. 6, 2005, issue of the New England Journal of Medicine. The same issue carried results of another study by Dr. Ridker, which showed that lowering CRP levels with statin drugs reduced the risk of a second cardiac event. (29, 30) back to top

The Role of Homocysteine

Another indicator of inflammation which may lead to heart disease is increased levels of homocysteine. Homocysteine is a common amino acid (one of the building blocks that make up proteins) found in the blood and is acquired mostly from eating meat. High levels of homocysteine are related to the early development of heart and blood vessel disease. In fact, it is considered an independent risk factor for heart disease. High homocysteine is associated with low levels of vitamin B6, B12, and folate, as well as kidney disease. Research has shown, however, that reducing your homocysteine levels with vitamins does not reduce your risk of heart disease. (37)

At elevated levels, homocysteine can block production of nitric oxide in the cells of the  blood vessel walls, making the vessels less pliable and allowing plaque to build up.(18) Levels of homocysteine greater than 15 µmol/L are predictive of increased mortality and morbidity. (8, 25, 18, 19, 20) A scientific advisory (18) from the American Heart Association on homocysteine, diet, and cardiovascular disease recommends screening for total homocysteine in high-risk patients with a personal or family history of premature cardiovascular disease. (8, 25)

Studies linking elevated homocysteine levels to heart disease have had mixed results, at best. Although elevated homocysteine has been associated with low folic acid, vitamin B6, and vitamin B12, supplementing with these nutrients does not seem to affect the frequency of cardiac events or number of deaths from heart disease. Thus, while elevated homocysteine may be associated with increased risk of heart disease, it appears that lowering homocysteine does not quickly repair the structure of damaged arteries or affect the course of the condition. (14, 16, 17, 18, 19)

What to Do

What should the prudent person do in order to reduce his or her risk of heart disease? For starters, manage your stress. Stress is a factor in elevating CRP and homocysteine. It activates the immune system in a “bad” way, makes hormone difficulties worse, and leads to increased inflammation. Next, find out if you have food sensitivities, and avoid the foods which lead to increased inflammation. Third, eat a diet rich in fiber, complex carbohydrates, and good quality protein, and moderate in fat. Stay tuned for the next newsletter…the final episode about cholesterol and heart disease will talk about different types of fats, the foods which contain them, and a summary to pull everything together. back to top


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