Higher Levels of Protein May Predict Heart Disease

March 30, 1999

A syndrome that scientists call the "metabolic syndrome"

and that the media often term "Syndrome X" may be associated with a low-level inflammatory reaction that predicts cardiovascular disease, a Wake Forest University scientist reported at an American Heart Association meeting in Orlando.

Results from a major national study demonstrate that low-level inflammation in adults is powerfully connected to measures of insulin metabolism, according to George Howard, professor of public health sciences (biostatistics and epidemiology) at the Wake Forest University School of Medicine.

The loss of sensitivity to insulin is believed to be a major cause of diabetes, and diabetes in turn is a major cause of heart disease. "Loss of insulin sensitivity is in part due to increased low-level inflammation," he said.

The metabolic syndrome includes high blood pressure, impaired glucose tolerance, obesity, lack of sensitivity to insulin, high levels of the bad cholesterol-- LDL and low levels of the good cholesterol, HDL

One marker of inflammation is a blood protein called C-reactive protein, and as it increases, risk of heart attacks increase, he said. When the C-reactive protein is in the high normal range, it indicates low level inflammatory status.

In a study called the Insulin Resistance Atherosclerosis study (IRAS), which involves diabetics and prediabetics, Howard analyzed the average level of C-reactive protein in the blood of 1,560 participants.

The level of C-reactive protein rose as blood sugar rose: from an average of 1.5 micrograms per milliliter for people with normal blood sugar, to an average of 2.6 micrograms per milliliter for people with impaired glucose tolerance and 3.2 for diabetics. Those with blood pressure within the normal range averaged 1.8 micrograms per milliliter compared to 3.0 for people with high blood pressure.

Howard said obesity, as measured by body mass index, also led to higher levels of C- reactive protein. "Just being obese can cause the system to become inflamed," he said

Those whose bodies are still sensitive to insulin averaged 1.2, while those who had developed resistance to insulin averaged 3.5 micrograms per milliliter.

"These results may provide an insight into a mechanism for several established cardiovascular risk factors," Howard said. In the IRAS study, at least, C-reactive protein "has strong associations with measures of the metabolic syndrome."

Interesting, he said, two long known risk factors for heart disease — cigarette smoking and increased thickness of the wall of the carotid artery — did not lead to increases in C-reactive protein.

Howard called for long term studies to determine where increased levels of the C-reactive protein in the blood predict heart attracks and strokes in people who have increased insulin resistance and diabetes.

The study was funded by the National Heart, Lung and Blood Institute.


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