C-reactive Protein (CRP) has transitioned from being considered solely an acute phase protein to an inflammatory marker (Yeh & Willerson, 2003). During infection or inflammation, circulating immune cells are recruited to the inflamed vessel. This happens by interacting with adhesion molecules. Although the level of adhesion molecules cannot be measured, the acute phase proteins and inflammatory cytokines in the blood can be assayed. In a study by Ridker, Hennekens, and Burns (2000), it was found that CRP surpassed all other biomarkers (including LDL levels) for predicting cardiovascular events. It is believed that the strong predictive values may be due to its long-term stability during storage (Yeh & Willerson, 2003). Because of its stability, CRP levels are not affected by food intake and demonstrate little or no circadian variations; hence there is no need for taking fasting blood samples (Ridker, 2003).

The name C-reactive Protein (CRP) was derived because it is a protein that binds to the C-polysaccharide of the pneumococcal cell wall (Tillett & Francis, 1930). It is a part of the immunity process that is activated by inflammation or infection. It has also been found to bind to phospholipids of damaged cells limiting uptake of the cells by macrophages (Mold, Gewurz, & DuClos, 1999). CRP has been found to amplify pro-inflammatory responses (Yeh, Anderson, Pasceri, et al., 2001). CRP has been found deposited in atherosclerotic plaques, and because of this, it is thought that CRP may promote the development of atherosclerosis (Reynolds & Vance, 1987).

C-reactive Protein: Risk Factor or Risk Marker

Risk factors are traditionally associated with a disease by virtue of their participation in causing the disease. Conversely, risk markers are statistically correlated with a disease without an established causal link (Pearson, Mensah, et al., 2003). Researchers have determined that inflammatory markers are potentially useful predictors of prevalence and incidence of cardiovascular disease (US Public Health Service, 1964; Pearson, Mensah, et al., 2003). However, professionals are cautioned regarding their consideration.

The distinction between CRP as a risk factor or risk marker has not yet been validated (Freinkel, 2003). The inflammatory response might be due to a reaction to other established cardiovascular disease risk factors, or simply a response to the disease itself. Thus, there is no current evidence supporting the belief that lowering CPR will necessarily reduce the relative risk of cardiovascular disease. It is however noteworthy to mention that many interventions reducing traditional risk factors for cardiovascular disease are also linked to lowering CRP levels. These include pharmacological therapies, as well as lifestyle changes, such as smoking cessation, weight loss, and physical activity (Ridker, 2003). Although more research needs to be conducted with respect to CRP as a risk factor, researchers have found that it can add prognostic information as a predictor of future cardiovascular events, as well as to lipid screening and evaluating metabolic syndrome (Schwartz, Boyes-Genis, et al., 2003).

C-reactive Protein: Traditional Assays versus hs-CRP Assays

The emphasis on highly-sensitive or high-sensitivity CPR (hs-CRP) seems to have created a false impression that it is measuring something different than previous assays for CRP. However, it is measuring the same C-reactive Protein. What has changed is the assay detection range to ensure the test is sensitive enough for detection of vascular disease (Pepys & Hirschfield, 2003).

Traditional assays for CRP did not have adequate sensitivity to detect levels required for vascular disease prediction. The prediction level resides somewhere in the range between 1.0 mg/L and 5 mg/L, which was regarded previously as the “normal” range (Yeh & Willerson, 2003). hs-CRP assays are widely available and the cost is comparable to standard cholesterol screening. Additionally, hs-CRP requires no special collection procedures. Due to it structure and its long half-life (18-20 hours), hs-CPR remains stable in fresh or frozen plasma and there is no need for the individual to fast prior to the assay.
C-reactive Protein: How to measure hs-CRP

To ensure within-individual variability, hs-CRP assays should be taken in a person without an inflammatory or infectious condition. The results should be expressed in mg/L only, and taken on 2 separate occasions, ideally 2 weeks apart. If the result is >10mg/L, then a source of infection or inflammation should be investigated.

Over the past decade, the pathophysiology of atherosclerosis has been linked to inflammatory response to injury (Libby, Ridker, & Maseri, 2003; Pearson, 2003; Schwartz, Bayes-Genis, et al., 2003). It appears that the initiation, growth, and complications of atherosclerosis are actually an inflammatory response that elevates CRP levels in the blood. According to Libby, Ridker, and Maseri (2002), there are many triggers for this inflammatory response that include lipoproteins, dyslipidemia, hypertension, diabetes, obesity, and infection or injury. This new evidence that supports the role of inflammation in the atherosclerotic process affirms the importance of inflammatory markers for risk stratification. Additionally, hs-CRP has been shown to predict future myocardial infarctions and strokes (Ridker, 2003).

C-Reactive Protein and Obesity

A great deal of research has been conducted on the relationship between lifestyle changes and the inflammatory response. These lifestyle factors include diet and weight loss. Obesity and physical inactivity are independent risk factors for cardiovascular disease and type 2 diabetes. Elevated levels of hs-CRP have also been associated with elevated body fat and high BMI levels (Esposito, Pontillo, et al., 2003). The results of these studies suggest that lowering body fat levels and reducing body weight is associated with lower circulating levels of inflammatory markers for future cardiovascular disease events. Esposita, Pontillo, et al. (2003) found this reduction in CRP was a resulted in improved insulin sensitivity and improvements in blood serum concentrations. In addition, Saito, Yonemasu, et al. (2003) found a significant correlation between elevated hs-CRP levels and weight gain, suggesting that weight loss may play an important role in reducing these levels.

C-reactive Protein and Metabolic Syndrome

Metabolic syndrome is a condition that describes an individual who is at high risk for diabetes and cardiovascular disease by virtue of exhibiting three or more associated risk factors. These risk factors include upper-body obesity, high levels of triglycerides, low HDL levels, high blood pressure, and abnormal glucose (Keller & Lemberg, 2003; Ridker, Buring, et al., 2003). Coincidentally, each of these risk factors is also positively correlated with elevated levels of hs-CRP (Keller & Lemberg, 2003). Elevated hs-CRP levels are also associated with insulin sensitivity (Ridker, Buring, et al., 2003). Although the results are inconclusive, baseline hs-CRP levels appear to be a strong predictor for metabolic syndrome, hence type 2 diabetes and cardiovascular disease.

C-reactive Protein and Type 2 Diabetes

Research suggests that hyperglycemia with associated elevated hs-CRP levels may serve to exacerbate the atherosclerotic process and thus help uncover severe cases of atherosclerosis (Verma, Wang, et al., 2003). Many empirical studies support the role of inflammation in the development of type 2 diabetes (Huerta & Nadler, 2002). These researchers found that elevated hs-CRP is positively correlated to type 2 diabetes. Other studies have found that elevated hs-CRP can be used as a strong predictor in non-diabetic patients who are at risk of developing the disease (Festa, D’Agostine, et al., 2002). These researchers suggest that elevated hs-CRP levels might be a better predicator than fasting glucose levels, independent of body fat and insulin resistance.

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