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Advancing the Assessment of Cardiovascular Risk
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"A role for inflammation has become well established over the past decade or more in theories describing the atherosclerotic disease process...virtually every step in atherogenesis is believed to involve cytokines, other bioactive molecules, and cells that are characteristic of infammation."
T. A. Pearson, et al. AHA / CDC Scientific Statement. Circulation. 2003.1
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After Libby, Ridker.
Circulation. 1999; 100: 1148-1150.2
>Click here for larger image.
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Published studies3,4 suggest cardiovascular disease (CVD) and peripheral vascular disease (PVD) are inflammatory processes, and can result in low levels of inflammatory markers, such as C-reactive protein. This finding, coupled with the availability of a number of assays, has fueled a lot of interest in identifying the most appropriate marker to help identify patients who are at risk for developing an acute ischemic event.
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Based on the findings from a number of studies, the National Cholesterol Education Program Adult Treatment Panel III (ATP III) Guidelines5 identified inflammatory markers as:
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Emerging risk factors |
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Useful as optional risk factor measurements for adjusting estimates of absolute risk obtained from standard risk factors |
The problem was that no consensus had been reached from professional societies or governmental agencies regarding how markers of inflammation should be used in clinical practice. In light of this, the Centers for Disease Control (CDC) and the American Heart Association (AHA) organized a meeting entitled “CDC / AHA Workshop on Inflammatory Markers and Cardiovascular Disease: Applications to Clinical and Public Health Practice.”2 The goals of this workshop were to find out:2
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Which of the currently available inflammatory markers should be used? |
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What results should be used to define high risk? |
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Which patients should be tested? |
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Indications for which tests would be most useful? |
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To investigate these questions, the panel members reviewed the scientific evidence between several inflammatory markers and explored the implications of an association between inflammatory markers and cardiovascular disease (CVD). Based on this analysis, they determined that:.2
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The comparison of various inflammatory markers favor CRP for assessment of inflammation |
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Within these lower, previously “normal” ranges, hs-CRP seems to have predictive abilities for CVD events |
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Studies of other, newer inflammatory markers such as interleukin-6 and SAA show similar results |
"In general, most studies show a dose-response relationship between the level of hsCRP and risk of incident coronary disease. Recent studies also suggest association with incidence of sudden death and peripheral arterial disease."
T. A. Pearson, et al. AHA / CDC Scientific Statement. Circulation. 2003.
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In light of this research, the CDC/AHA made the following recommendations:2
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Of the current inflammatory markers compared for potential clinical use, hsCRP has the analyte and assay characteristics most conducive to use in practice, with a precision < 0.3 mg/L. Other inflammatory markers (cytokines and other acute phase reactants) should not be measured for the determination of coronary risk in addition to hsCRP. |
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The entire adult population should not be screened with hsCRP. Measurements of hsCRP may be used at the discretion of the physician as part of a global coronary risk assessment in adults without known CVD. In those patients judged to be at intermediate risk (10% to 20% risk of CHD over 10 years), hsCRP may help direct further evaluation and therapy in the primary prevention of CVD. This assumes assessment of traditional cardiovascular risk factors and the calculation of an absolute risk score before measurement of hsCRP. |
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The workshop also concluded that hsCRP levels may be useful in motivating patients to improve lifestyle behaviors. |
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Based on distributions of hsCRP samples from > 15 populations and > 40,000 persons, the following cut points were identified:
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| Relative Risk Category and Average hs-CRP Level2 |
| Low risk < 1.0 mg/L |
| Average risk 1.0 – 3.0 mg/L |
| High risk > 3.0 mg/L |
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As the original diagnostic licensee of the Brigham and Women's Hospital patent for hsCRP, the Siemens hsCRP assay was the method featured in many highly significant studies6 and has been used for comparison in many published studies to date.6,7 The Siemens CardioPhase® hsCRP assay is the first to have a cardiac specific claim as an independant marker for risk assessment and risk stratification. For more information on CardioPhase® hsCRP click here.
As the table and chart show, hsCRP provides prognostic information at all levels of LDL cholesterol.6,8
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Relative Risk Estimates of Future Coronary Events6
Quintile of
TC:HDL-C Ratio |
Quintile of N hsCRP (mg/L) |
| 1 |
2
(< 0.7) |
3
(0.7-1.1) |
2
(1.2-1.9) |
2
(2.0-3.8) |
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Men |
Women |
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| 1 |
< 3.4 |
< 3.4 |
1.0 |
1.2 |
1.4 |
1.7 |
2.2 |
| 2 |
3.4-4.0 |
3.4-4.1 |
1.4 |
1.7 |
2.1 |
2.5 |
3.0 |
| 3 |
4.1-4.7 |
4.2-4.7 |
2.0 |
2.5 |
2.9 |
3.5 |
4.2 |
| 4 |
4.8-5.5 |
4.8-5.8 |
2.9 |
3.5 |
4.2 |
5.1 |
6.0 |
| 5 |
> 5.5 |
> 5.8 |
4.2 |
5.0 |
6.0 |
7.2 |
8.7 |
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Relative risk and TC: HDL-C ratio were derived from N Engl J Med. 1997; 336: 973-979 and N Engl J Med. 2000; 342: 836-843. hsCRP estimates were derived from ongoing population-based surveys.
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After Libby, Ridker.
Circulation. 2003; 107: 363-369.8
>Click here for larger image.
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Predicting Long-Term Cardiovascular Risk
These data show that C-Reactive Protein is a sensitive marker for underlying vascular inflammation which may be clinically useful in the prediction of future MI, stroke and peripheral vascular disease.6,8,9
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When used in conjunction with other markers of risk, it can help predict cardiovascular risk among:3,8,10
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Healthy men and women at risk for first-ever vascular events |
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High-risk individuals with stable/unstable angina |
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Individuals with prior MI |
To review data from numerous clinical studies of hs-CRP as a risk factor for future cardiovascular events, click here. These studies demonstrate that low concentrations of hs-CRP may indicate a silent atherosclerosis before a cardiovascular event occurs.3
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References
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