Move Over Cholesterol, Inflammation Is Taking Over

Inflammation has been identified as a significant factor in the development of coronary artery disease, plaque instability, and plaque rupture. New parameters to assess risk and identify specific markers have affected how we diagnose—and treat—both stable and unstable heart disease processes.

It’s Not Just Cholesterol Anymore

It used to be thought that cholesterol alone was the major marker for atherosclerosis. This is no longer the case.

Pro-inflammatory messengers, referred to as cytokines, are only now being recognized as behind-the-scenes culprits. These cytokines are chemicals produced by the body that are similar to hormones, acting on tissues or organs far from the site of secretion.

When inflammation is present, interleukin-1 and tumor necrosis factor alpha induce cytokine messengers such as interleukin-6 to instruct the liver to increase inflammatory mediators.

The resulting substances, such as C-reactive protein (CRP) and serum amyloid A, are released into the blood. It is at that point that they serve as measures of underlying chronic inflammation.

CRP Is Indicative of Cardiac Risk

C-reactive protein is easily measured in a routine blood test and is known as a marker for inflammation that is directly associated with atherosclerotic plaque. In multiple studies, C-reactive protein has been identified as a potent predictor of future cardiovascular events for otherwise healthy men and women—one that’s far more reliable than elevated cholesterol levels.

Here are the highlights from a study of CRP in 28,000 American women. Researchers looked at CRP and LDL levels in women who developed coronary artery disease and put them into one of four possible categories:

• High CRP/High LDL cholesterol;
• High CRP/Low LDL cholesterol;
• Low CRP/High LDL cholesterol; and
• Low CRP/Low LDL cholesterol.

The results were quite surprising. Most cardiologists would have expected that women with higher levels of LDL would have been at the highest risk. But in this large study, not only was elevated CRP the best indicator of risk, women with high LDL and high CRP were also at the MOST risk. This is because inflammation is prompting the LDL to oxidize and form into plaque, rather than circulate freely.

This finding is significant, as this study shows once again that LDL cholesterol is not the lone culprit in coronary artery disease. In fact, this study reported that out of 12 possible risk factors, elevated CRP was the strongest predictor of future cardiac events for postmenopausal women. And, by the way, high CRP levels also predicted greater risk for men.

Interleukin-6 May Be An Even Greater Predictor

Next, let’s look at results from the Iowa 65+ Rural Health Study, where investigators studied interleukin-6. (Interleukin-6 stimulates the liver to produce CRP in the first place.)

The Iowa study demonstrated that elevations of interleukin-6 and CRP were associated with increased risk of both cardiovascular disease and general mortality in healthy older people. In another project—the large Physicians Health Study (PHS)—higher levels of CRP were found to predict risk for heart attack and ischemic (low blood oxygen) stroke in men.

Biological characteristics that are associated with high CRP levels include infections, high blood sugar, overweight status, and stickiness of the blood. Any one of these situations literally feeds pro-inflammatory mediators, ratcheting up the chances that you’ll develop atherosclerosis.

Therefore, whether you are talking CRP or interleukin-6, stopping inflammation is the key to stopping atherosclerosis, heart disease, and even sudden cardiac death.

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