More than 800,000 individuals suffer a myocardial infarction annually in the US, and another 700,000 experience a stroke.1
Of these events, nearly half occur in patients with no overt evidence of hyperlipidemia and 15% to 20% occur in patients with none of the major traditional risk factors.2,3
At the opposite end of the spectrum, a disproportionate number of events occur in individuals with a history of myocardial infarction, indicating the high level of risk for recurrent events in these patients.
Although half of women and two-thirds of men in the US are affected by cardiovascular disease (CVD) after the age of 40,1, 4
only a small proportion of asymptomatic adults (<1% of women and approximately 5% of men) are classified as at `high risk' for CVD using contemporary risk scores. This discrepancy has been coined the `detection gap'.5
In the US, 10% of asymptomatic women (~7 million) and 40% of asymptomatic men (~26 million) are considered to be at intermediate risk.5, 6
As the level of risk determines the intensity of preventive interventions, there is a clear need for better risk assessment in asymptomatic individuals, particularly those at intermediate risk.
The National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III guidelines7
provide a global risk score for `hard' coronary heart disease (CHD) events (myocardial infarction and death caused by coronary heart disease), and the 1998 Framingham risk score equation estimates total CHD events (myocardial infarction, cardiac death, coronary insufficiency);8, 9
a 10-year absolute risk of a hard coronary event less than 10% is considered to be low risk, 10-20% is intermediate risk, and greater than 20% is high risk.7
It has been proposed that the intermediate risk category be extended to include individuals who have a 10-year absolute risk between 5% and 20%. Proponents of this change argue that this lower cut-off identifies a group of individuals, especially women, who could gain more benefit from aspirin and more aggressive lipid-lowering therapy and lifestyle modification than those with 10-year absolute risk of less than 5%.5, 10
Increasingly, the intermediate risk category is being further divided into `low' and `high' subgroups (i.e. 5-<10% and ≥10-<20%).
Numerous biomarkers have been proposed for improving CVD risk prediction. A biomarker is felt to be useful if the following criteria are met: it adds to clinical knowledge; it provides risk information that is independent of established predictors; it is easy to measure and interpret in a primary care setting; it is accurate, reproducible and internationally standardized; and it has a favorable cost-benefit ratio.11
Screening biomarkers should also improve patient management, particularly through more accurate risk classification and guidance in choice of therapy.11
C-reactive protein (CRP) is an easily measured and widely investigated biomarker of inflammation. The link between inflammation and atherosclerosis is well established; inflammation is a key element of the atherosclerotic process, contributing to all of its stages (initiation, growth, and plaque rupture).12-14
Thus, it would not be surprising if serum levels of inflammatory markers such as CRP improve prediction of CHD and stroke risk in at least some patient populations.
Although a number of Reviews related to the high-sensitivity CRP test (hsCRP) have been published in recent years, no review has comprehensively addressed the relevance of hsCRP in a variety of scenarios encountered in clinical practice—primary prevention of CVD, stroke and diabetes mellitus, and secondary prevention of CVD. We summarize the available data and assess whether they support proposed guidelines for clinical hsCRP measurement. We will consider CRP as a means to improve risk stratification and enable a better match between therapy and level of risk, not as a therapeutic target in its own right. Data are lacking as to whether CRP reduction per se reduces cardiovascular risk independent of other modifiable risk factors.