"The study provides further conclusive evidence that C-reactive protein, until now viewed as an innocent bystander in the formation of heart disease, is in fact a key culprit that causes inflammation in the arteries, resulting in formation of clots and plaque that lead to heart attacks and strokes," said Ishwarlal Jialal, M.D., lead author.

In the current study, investigators showed that C-reactive protein causes aortic endothelial cells to produce higher levels of an enzyme that inhibits the breakdown of clots, plasminogen activator inhibitor-1. The enzyme is known as a strong risk marker for heart disease, especially in people with diabetes. After C-reactive protein activated endothelial cells to produce the enzyme, precursors to plaques and blood clots developed.

High C-reactive protein levels can occur in otherwise clinically healthy individuals, Jialil said. Patients with high levels can reduce protein levels and cardiovascular risk by losing weight, exercising regularly, using a statin drug, and stopping cigarette smoking.

The study also examined the links between C-reactive protein and plasminogen activator inhibitor-1 and metabolic disorders.

"… this study shows that in the presence of high blood-glucose levels, C-reactive protein is especially active in the stimulation of plasminogen activator inhibitor-1. As a result, the effect of C-reactive protein is especially acute for patients with diabetes and metabolic syndrome," said Sridevi Devaraj, study coauthor. "Given the current pandemic of obesity which increases one's risk of diabetes, the study's insights about the active role of C-reactive protein and plasminogen activator inhibitor-1 in heart disease are especially valuable."

The authors stress that the current findings point to the multiple ways in which C-reactive protein may be a direct contributor to the development of cardiovascular disease and thromboembolic events, especially in people with metabolic dysfunction.