Biomarkers of Inflammation in Atherosclerosis


Russell P. Tracy
University of Vermont
Colchester, VT, USA

Dr. Tracy took a population-based approach to his discussion of correlation of markers of inflammation with risk for cardiovascular disease. He mentioned three types of markers: systemic ones including C-reactive protein and fibrinogen, systemic and local mediators, and cell adhesion markers. Most of his discussion centered on C-reactive protein. He concluded that many biomarkers may be valid risk predictors and the choice for clinicians may depend more on technical factors such as standardization and sensitivity and specificity than correlation of marker and risk for cardiovascular disease.

Dr. Tracy took a population-based approach, citing studies that have examined possible biomarkers of inflammation such as systemic markers, systemic and local mediators, and cell adhesion markers. His focus was largely on C-reactive protein. However, he asserted that final choices of marker(s) for use in the clinical setting will probably depend more on technical factors such as standardization and sensitivity and specificity than the validity of the association between an individual marker and cardiovascular risk.

He discussed two prospective studies on C-reactive protein level and cardiovascular disease. In one study, C-reactive protein levels were obtained from healthy young adults. Ten years later, subjects were screened for coronary calcifications. Individuals who had ranked in the third quartile for protein level at year five were twice as likely to have evidence of calcification. In a study of older men, ranking in the highest quartile for C-reactive protein predicted a three-fold increase in short-term risk for myocardial infarction compared with risk for subjects in the lowest quartile.

The C-reactive protein biomarker is valid for relative risk for signs of atherosclerosis (calcification in younger adults, infarction in older people), but it reflects only the inflammatory aspect of the disease. If lipid-related risk is charted on one axis, the protein on a second, and relative risk on the third (vertical) axis, a depiction is obtained that Dr. Tracy feels is probably most valid in presenting relative risk. Analysis shows that 0 risk is obtained at lipid levels of roughly 140 total cholesterol and 80 LDL cholesterol. Maintenance of such levels in mice does result in suppression of atherosclerosis.

Because researchers do not understand the biology underlying the association between lipids, inflammatory markers, and cardiovascular disease, they look for correlations between known risk factors and biomarker elevation. Elevated C-reactive protein levels have been correlated with numerous risk factors. General correlation with metabolic disorders including hypertension, hyperglycemia, and obesity, as well as correlation between degree of elevation and number of metabolic disorders present in an individual, has several implications. First, markers in older people, who have a higher likelihood of comorbidity along with cardiovascular disease, are more likely to be nonspecific for cardiovascular disease. Second, change in marker level over time may reflect development or progression of one or more disease processes.

One effort to make biomarkers more specific for cardiovascular disease involves definition of a joint marker, such as C-reactive protein and fibrinogen. Ranking in the highest quartile for both markers identified 13% of study subjects compared with 25% with use of only one marker. In addition, analysis showed that rank in the highest quartile for both markers placed older people at 20-fold short-term relative risk for infarction compared with the risk for people placing in the lowest quartile for both.


Reporter: Elizabeth Coolidge-Stolz, MD