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LE Magazine May 2003

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Predict Your Risk of Future Disease

The verdict is in. It is C-reactive protein, and not cholesterol that puts people at their greatest risk for developing heart disease, stroke and other age-related ailments.

C-reactive protein is an inflammatory marker produced in response to acute injury, infection or other inflammatory stimuli. Chronically elevated levels of C-reactive protein can reveal a state of systemic inflammation that causes or contributes to many different kinds of lethal diseases.

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The most immediate danger of chronic inflammation is that it induces plaques along arterial walls to become more vulnerable to rupture.1 When an atherosclerotic plaque ruptures, it releases chunks of tissue that may then become lodged in the arteries that feed the heart muscle, or in the vessels that oxygenate brain cells. The end result is a heart attack or stroke as blood vessels become choked from lack of oxygen.

A C-reactive protein blood test can serve to reveal the existence of vascular disorders in their earliest stages, so that appropriate anti-inflammatory therapies can be administered to lower C-reactive protein expression.

The following new studies provide examples of the different disorders associated with elevated C-reactive protein:

  1. C-reactive protein is elevated in those who suffer from Alzheimer's disease, and high levels have also been correlated with loss of cognitive ability in seemingly healthy people. One study published in the January 2003 issue of the Journal of Neuroimmunology found that in a healthy population from the Netherlands, C-reactive protein levels at the study's outset were predictive of poorer scores on a test of learning and recall during the six years of the study's follow-up.2
  2. Elevated inflammatory markers are characteristic of type II diabetes. Dr. Paul Ridker, who has conducted many of the studies that support C-reactive protein's relationship to chronic age-related disease, indicates that the extent of the inflammatory process known to exist in diabetics can be measured with the C-reactive protein test.3
  3. Some evidence indicates that C-reactive protein elevation could be linked with depression in aging people, which may at least partially explain why chronic depression increases heart disease risk in this population. In the December 2002 issue of the American Journal of Cardiology, researchers at Washington University in St. Louis, Missouri reveal that depressed subjects exhibited significantly higher levels of C-reactive protein and other markers of inflammation than did subjects who were not depressed. The depressed patients were also more likely to be obese-not surprising, in light of the fact that obesity causes elevations in C-reactive protein as well.4
  4. Smoking, high blood pressure and the use of synthetic female hormones (in the form of oral contraceptives or hormone replacement therapy)-all of which increase the risk of adverse cardiovascular events-also have been found to cause elevations in C-reactive protein levels.

Consensus is building that C-reactive protein measurements are superior to any type of blood test when it comes to predicting the risk of heart disease or stroke. It follows that C-reactive protein measurement should be added to the usual blood tests administered to assess such risks.

The reason most people consider blood testing is to ascertain their cardiovascular risk factors. It has become evident that prediction of heart disease risk goes far beyond cholesterol counts and blood pressure measurements.

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Most physicians still do not routinely test for C-reactive protein, despite the fact that it is inexpensive and highly accurate. Instead, they continue to base evaluations of cardiac risk on traditional measurements of LDL/HDL cholesterol and triglycerides. While there is a place for these measurements in the overall scheme of laboratory testing for cardiac disease prevention, they should by no means stand alone. (Tests to evaluate homocysteine and fibrinogen are also important for those who wish to gain an accurate picture of what's going on inside their arteries.)

Neglecting to test levels of this inflammatory marker once a year could rob you of the chance to take early, aggressive steps to reverse the cardiac disease processes.

What causes elevated C-reactive protein

While some doctors are finally catching on to the fact that elevated C-reactive protein increases heart attack and stroke risk, they still know little about its other dangers. Even fewer practicing physicians understand that pro-inflammatory cytokines are an underlying cause of systemic inflammation that is indicated by excess C-reactive protein in the blood.

In an abstract published in the March 6, 2002 issue of the Journal of the American College of Cardiology5, tumor necrosis factor-alpha (TNF-a) levels were measured in a group of people with high blood pressure and a group with normal blood pressure. The objective of this study was to ascertain if arterial flow mediated dilation was affected by hypertension and chronic inflammation as evidenced by high levels of the pro-inflammatory cytokine TNF-a.

The hypertensive subjects taking anti-hypertensive medications had about the same blood pressure as the healthy test subjects. Arterial flow mediated dilation, however, was significantly impaired in the hypertensives and this group also showed higher levels of TNF-a, indicating persistent inflammation despite blood pressure control. This study showed that even when blood pressure is under control, hypertensives still suffer from continuous damage (endothelial dysfunction) to the inner lining of the arterial wall caused by a chronic inflammatory insult. The doctors who conducted this study concluded by stating: "Antihypertensive therapy alone may be insufficient to improve endothelial dysfunction in hypertensives with high plasma levels of inflammatory markers. Additional therapy to target inflammation may be necessary to improve endothelial function and to prevent progression of coronary atherosclerosis in high-risk hypertensives with subclinical inflammations."

These findings indicate that hypertensives should have their blood tested for TNF-a to assess how much inner wall (endothelial) arterial damage is occurring. If the level of TNF-a is high, aggressive therapies to suppress the inflammatory cascade should be considered.

Elevated C-reactive protein and interleukin-6 predict type II diabetes
In a study published in the July 18, 2001 issue of the Journal of the American Medical Association (JAMA)6, a group from the famous Women's Health Study were evaluated to ascertain what risk factors could predict future development of type II diabetes. The findings showed that baseline levels of C-reactive protein and interleukin-6 (IL-6) were significantly higher among those who subsequently developed diabetes compared to those who did not.

When comparing the highest versus lowest quartile, women with the higher IL-6 levels were 7.5 times more likely to develop diabetes while those in the higher C-reactive protein ranges were 15.7 times more likely to become diabetic. After adjusting for all other known risk factors, women with the highest IL-6 levels were 2.3 times at greater risk, while those with the highest C-reactive protein levels were 4.2 times more likely to become diabetic. It should be noted that these other diabetic risk factors (such as obesity, estrogen replacement therapy and smoking) all sharply increase inflammatory markers in the blood. The doctors who conducted this study concluded that, "Elevated C-reactive protein and IL-6 predict the development of type II diabetes mellitus. These data support a possible role for inflammation in diabetogenesis."

C-reactive protein and IL-6 predict death

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It is well established that elevated C-reactive protein, IL-6 and other inflammatory cytokines indicate significantly greater risks of contracting or dying from specific diseases (heart attack, stroke, Alzheimer's disease, etc.)

A group of doctors wanted to ascertain if C-reactive protein and IL-6 could also predict the risks of all-cause mortality. In a study published in the American Journal of Medicine7, a sample of 1,293 healthy elderly people were followed for a period of 4.6 years. Higher IL-6 levels were associated with a two-fold greater risk of death. Higher C-reactive protein was also associated with a greater risk of death, but to a lesser extent than elevated IL-6. Subjects with both high C-reactive protein and IL-6 were 2.6 times more likely to die during follow-up than those with low levels of both of these measurements of inflammation. These results were independent of all other mortality risk factors. The doctors concluded by stating:

"These measurements (C-reactive protein and IL-6) may be useful for identification of high-risk subgroups for anti-inflammatory interventions."

Frailty in elderly linked to inflammation

In a study of almost 5,000 elderly people, scientists discovered that frail seniors were more likely to have signs of increased inflammation than their more active counterparts. This study was published in the Archives of Internal Medicine8 and showed that these frail seniors with elevated blood inflammatory markers also tend to show more clotting activity, muscle weakness, fatigue and disability than active elderly people.

Findings from these studies should motivate every health conscious individual to have their blood tested for C-reactive protein. If it is elevated, then the Inflammatory Cytokine Test Panel is highly recommended. Those who suffer from any type of chronic disease may also consider the Inflammatory Cytokine Test Panel in order to identify the specific inflammatory mediator that is causing or contributing to their problem.

Continued on Page 2 of 2

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