We should note that “inflammation” as the term is used here does not mean the full form of the condition (warmth, redness, swelling, and pain), but rather implies a “micro-inflammation.” A person with this condition is characterized by being in the upper part of the “normal” distribution for inflammation status, without the signs and symptoms of overt, clinical inflammation. Molecular epidemiology has played a key role in identifying the role of inflammation in CVD, and recently it has become clear that inflammation is connected to the metabolic syndrome in a complex and important manner. Link
Acute-phase proteins are a class of secreted proteins, primarily from the liver, that either rise or fall in concentration in response to inflammatory stimuli, such as tissue damage and infection. This change in most cases represents no more than a doubling or tripling in concentration (eg, fibrinogen) or a 30 to 50% decrease (eg, albumin). A few of the known proteins, such as C-reactive protein (CRP), may increase in concentration > 1,000-fold. Virtually all of the proteins that have been studied have been shown to be associated with CVD (Table 2). Most of the known acute-phase proteins are produced in the liver in response to IL-6. Although these markers have many different functions, they all are moderately to strongly associated with the presence of CVD (in all cases clinical CVD; in some cases subclinical CVD as defined by such techniques as carotid artery ultrasonography); in almost every case, an argument can be made—at least hypothet-ically—that the protein in question is not only a marker of the process but might also participate in the process.
In population studies or clinical research, inflammation is usually estimated by the measurement of a plasma acute-phase protein, such as CRP or fibrinogen.
Table 2—Acute-Phase Reactants Associated With CVD
|Acute-Phase Reactants||Proposed Mechanisms|
|Fibrinogen||Increased coagulant activity; decreased fibrinolysis due to increased clot density; increased platelet aggregation; increased plasma viscosity|
|Factor VIII||Increased coagulant activity|
|CRP||Increased tissue factor expression on monocytes; increased cell adhesion molecule-mediated cell attachment to endothelial cells; increased complement activation|
|Ceruloplasmin||Increased oxidative damage due to higher plasma copper levels|
|PAI-1||Decreased fibrinolytic potential; decreased plaque cellularity|
|Serum amyloid A||None proposed to date|
|Ferritin||Increased oxidative damage due to higher plasma iron levels|
|a:-acid glycoprotein||None proposed to date|
|Albumin||Decreased antioxidation due to decreased plasma bilirubin level|
|High-density lipoprotein||Increased low-density lipoprotein levels due to decreased removal of tissue cholesterol|