A recent study involving over 27,000 women conducted at Brigham and Women's Hospital in Boston, Massachusetts, suggests that the C-reactive protein (CRP) level may be a stronger indicator of future cardiovascular incidents than the low-density lipoprotein (LDL) cholesterol level (1). Previous studies have alluded to CRP's growing value in coronary health assessment; however, none have captured headlines to this degree before now. For example, several studies have reported that a high level of the plasma inflammation biomarker (CRP) is a strong independent predictor of future coronary complications (1-4) and others (5-7) have suggested that higher than normal CRP levels are a "moderately strong risk factor" (5) for cardiovascular disease.
The series of events that increase CRP levels begin with a tissue injury or infection, causing the release of cytokines (2). These cytokines proceed to the liver, where they induce the synthesis and release of CRP into the blood stream (2,8). Whether CRP serves primarily as an indirect risk factor (acting as an index of inflammation (1-3,5-7)) or as a direct risk factor (by contributing to atherogenic activity and tissue damage (2,4,9)) is still in question. Normal plasma CRP levels are usually 0 to less than 1 mg/ml (9). Researchers have found that when plasma CRP levels are greater than 3.6 mg/ml in those with stable angina, the risk of some form of cardiovascular episode occurring has a 2-fold increase (9). One in vitro study reported that CRP provides a direct proantherogenic effect on human endothelial cells by inducing the expression of adhesion molecules (9). Other deleterious effects of CRP on which scientists have speculated include an upregulation of proinflammatory cytokines within existing lesions (5), binding to lipoproteins, which may trigger complement activation and subsequent inflammation (2), and interfering with macrophage LDL uptake, which may lead to increased foam cell synthesis (5).
The potential correlation between cardiovascular disease risk and plasma CRP has investigators exploring possible approaches for maintaining healthy CRP levels. In a recent study involving 57 subjects with type II diabetes, individuals were randomized to receive tomato juice, vitamin E, vitamin C, or a placebo for four weeks (10). Based on their results, researchers discovered the potential for vitamin E to maintain healthy CRP levels (10). Furthermore, a study conducted at the University of Texas reported that vitamin E supplementation promoted healthy CRP and cytokine metabolism (11).
As suggested by the Brigham and Women's study published in the New England Journal of Medicine and others studies, CRP may become an important, routine factor for assessing cardiovascular risk. Much remains unknown about the effects of CRP, but the puzzle will continue to be pieced together with additional research. Vitamin E is an important antioxidant for cardiovascular health. Preliminary findings suggest that it may play a role in maintaining healthy CRP and cytokine function.
1) Ridker PM, Rifai N, Rose L, Buring JE, and Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. New England Journal of Medicine. 2002; 347(20): 1557-65.
2) Lagrand WK, et al. C-Reactive Protein as a Cardiovascular Risk Factor: More Than an Epiphenomenon? Circulation. 1999; 100: 96-102.
3) Ridker PM. High-Sensitivity C-Reactive Protein: Potential Adjunct for Global Risk Assessment in the Primary Prevention of Cardiovascular Disease. Circulation. 2001; 103: 1813-1818.
4) Jialal I, Devaraj S. Inflammation and atherosclerosis: the value of the high-sensitivity C-reactive protein assay as a risk marker. American Journal of Clinical Pathology . 2001; 116 Suppl: S108-15.
5) Folsom AR, et al. C-Reactive protein and incident coronary heart disease in the Atherosclerosis Risk In Communities (ARIC) study. American Heart Journal . 2002; 144: 233-238.
6) Wang TJ, et al. C-Reactive Protein Is Associated With Subclinical Epicardial Coronary Calcification in Men and Women: The Framingham Heart Study. Circulation . 2002; 106:1189-1191.
7) Pradhan AD, et al. Inflammatory Biomarkers, Hormone Replacement Therapy, and Incident Coronary Heart Disease: Prospective Analysis From the Womens Health Initiative Observational Study. JAMA. 2002; 288: 980-987.
8) Vander A, Sherman J, Luciano D. 2001. Human Physiology: The Mechanisms of Body Function . 8th ed. New York: McGraw-Hill.
9) Pasceri V, Willerson JT, and Yeh ETH. Direct Proinflammatory Effect of C-Reactive Protein on Human Endothelial Cells. Circulation. 2000;102: 2165-2168.
10) Upritchard JE, Sutherland WHF, and Mann JI. Effect of Supplementation with Tomato Juice, Vitamin E, and Vitamin C on LDL oxidation and Products of Inflammatory Activity in Type 2 Diabetes. Diabetes Care. 2000; 23(6): 733-738.
11) Devaraj S and Jialal I. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Radical Biological Medicine. 2000; 29(8): 790-2.
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