CHAPEL HILL — Heart attack survivors who suffer advanced gum disease show significantly higher levels of a protein in their blood called C-reactive protein (CRP) than such patients without gum disease, new University of North Carolina at Chapel Hill research indicates.

The findings, presented Sunday (Nov. 12) during a news conference at the annual American Heart Association meeting in New Orleans, suggest that the presence of gum disease might increase the risk of a second heart attack in people with a history of heart disease.

“Not only did the heart attack patients with periodontal disease have higher levels of CRP than those without gum disease, but the CRP levels were directly related to the severity of the gum disease,” said Dr. Efthymios N. Deliargyris, an interventional cardiologist and a member of the Center for Oral and Systemic Diseases at UNC-CH. “The more severe the gum disease, the higher the CRP levels.”

Besides Deliargyris, also an instructor in medicine at the UNC-CH School of Medicine, study investigators were Drs. Steven Offenbacher, professor of periodontology and center director, James D. Beck, professor of dental ecology, both at the UNC-CH School of Dentistry, and Sidney C. Smith Jr., chief of cardiology and past president of the American Heart Association.

“We know a lot of risk factors for heart attacks, including high blood pressure, high cholesterol, diabetes and cigarette smoking, but all those combined only explain about two-thirds of heart attacks,” Deliargyris said. “Since about a third of people who suffer heart attacks don’t have those risk factors, there’s a wide search going on for other conditions that may contribute to increased risk.”

Studies at UNC-CH and elsewhere have linked periodontal disease — an advanced form of gingivitis — with increased risk of heart attacks, but it has been unclear what the two conditions have in common, the physician said.

“The one thing we know the two conditions share is that they tend to initiate an immune response, also called an inflammatory response, in the body,” he said. “The most common marker for this response is this C-reactive protein, which is considered predictive of future adverse events like heart attack.”

To learn how common severe gum disease was in heart attack victims, the UNC-CH team conducted their pilot study of 38 heart attack patients and matched them with a comparable group of 38 other people without known heart disease. Researchers found a high percentage of the former had periodontal disease — 85 percent — as compared with only 29 percent of the controls.

“The most exciting finding was that among people with a heart attack, those with periodontal disease had much higher CRP levels than those with a heart attack but no periodontal disease,” Deliargyris said. “It seems that the presence of periodontal disease on top of a heart attack has a synergistic effect and a very accentuated CRP release.”

Despite its small size, the study findings are the first of their kind and potentially very important, he said.

“This gives us an insight into possible mechanisms underlying the association between gum disease and heart disease,” Deliargyris said. “Now we believe that patients with a heart attack and periodontal disease have an exaggerated inflammatory response with higher CRP levels that might put them at risk for future heart attacks. This work also raises the possibility that by treating severe gum disease in people with heart attacks, we might be able to reduce their CRP levels and their risk of another heart attack.”

By DAVID WILLIAMSON
UNC News Services

———————————————————————————————–

Heart Disease

Several theories exist to explain the link between periodontal disease and heart disease. One theory is that oral bacteria can affect the heart when they enter the blood stream, attaching to fatty plaques in the coronary arteries (heart blood vessels) and contributing to clot formation. Coronary artery disease is characterized by a thickening of the walls of the coronary arteries due to the buildup of fatty proteins. Blood clots can obstruct normal blood flow, restricting the amount of nutrients and oxygen required for the heart to function properly. This may lead to heart attacks.

Another possibility is that the inflammation caused by periodontal disease increases plaque build up, which may contribute to swelling of the arteries.

Researchers have found that people with periodontal disease are almost twice as likely to suffer from coronary artery disease as those without periodontal disease.

Periodontal disease can also exacerbate existing heart conditions. Patients at risk for infective endocarditis may require antibiotics prior to dental procedures. Your periodontist and cardiologist will be able to determine if your heart condition requires use of antibiotics prior to dental procedures.

Stroke

Additional studies have pointed to a relationship between periodontal disease and stroke. In one study that looked at the causal relationship of oral infection as a risk factor for stroke, people diagnosed with acute cerebrovascular ischemia were found more likely to have an oral infection when compared to those in the control group.

UC Davis study identifies C-reactive protein as cause of blood clot formation

(SACRAMENTO, Calif.) — Further underscoring the limitations of cholesterol screening in assessing a patient’s risk for heart disease, a new study by UC Davis physicians is the first to conclusively link C-reactive proteins (CRP) to formation of blood clots, a major cause of heart attacks, strokes and other vascular disease. Until now, CRP had been recognized mainly as a risk marker of heart disease. The study appears in the Jan. 25 print edition of the journal Circulation, a publication of the American Heart Association, and is available on the Web at www.circulationaha.org. 

“The study provides further conclusive evidence that CRP, 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, professor of pathology and director of the Laboratory for Atherosclerosis and Metabolic Research at UC Davis School of Medicine and Medical Center.

The study demonstrates that CRP causes cells in the arteries, known as human aortic endothelial cells, to produce higher levels of an enzyme that inhibits the breakdown of clots. The enzyme, plasminogen activator inhibitor-1 (PAI-1) is also a strong risk marker for heart disease, especially in diabetics. The study used a variety of techniques to convincingly show how CRP activates PAI-1 in aortic cells, causing lesions in the arteries that ultimately lead to formation of plaque and blood clots.

The study underscores the need to use CRP screening to more accurately assess at-risk populations, according to Jialal, who is the Robert E. Stowell Endowed Chair in Experimental Pathology.

“Based on these findings, if a patient has normal cholesterol but high levels of CRP, an aggressive course of treatment is recommended to help the patient reduce the risk of heart attack, stroke and other heart diseases,” said Jialal. “By relying on cholesterol alone, a physician could significantly underestimate a patient’s risk level.”

High CRP levels can occur in otherwise healthy individuals, according to the study. Patients with high levels of CRP can reduce risk by losing weight, exercising on a regular basis, stopping cigarette smoking, or taking statin drugs, Jialal added.

The study also closely links CRP and PAI-1 to diabetes and metabolic syndrome, a disorder characterized by a disproportionate amount of abdominal fat, elevated blood pressure, blood sugar and triglycerides and low levels of HDL, the “good” kind of cholesterol.

“In another important discovery, this study shows that in the presence of high blood-glucose levels, CRP is especially active in the stimulation of PAI-1. As a result, the effect of CRP is especially acute for patients with diabetes and metabolic syndrome,” said Sridevi Devaraj, a co-investigator and assistant professor of pathology at UC Davis. “Given the current pandemic of obesity which increases one’s risk of diabetes, the study’s insights about the active role of CRP and PAI-1 in heart disease are especially valuable.”

The new study adds to the findings of another landmark study on CRP by Jialal’s team at UC Davis that showed CRP actually damages the blood vessel wall by blocking a critical “protector” protein and inhibiting nitric oxide.

“Interestingly, the new study indicates that activation of PAI-1 was unrelated to the nitric oxide inhibition identified in the earlier study,” said Jialal. “This indicates that CRP has multiple, independent effects that cause heart disease.”

Dan Yan Xu, a physician and postgraduate researcher in the pathology department at UC Davis, also contributed to the study.

This study was supported by grants from the National Institutes of Health, the Juvenile Diabetes Foundation and American Diabetes Association.