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Evaluating Novel Cardiovascular Risk Factors: Can We Better Predict Heart Attacks?

Paul M. Ridker, MD, MPH
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From Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Ann Intern Med. 1999;130(11):933-937. doi:10.7326/0003-4819-130-11-199906010-00018
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Myocardial infarction often occurs among persons without traditional risk factors, and it has been hypothesized that assessment of “novel” markers may help identify persons who are prone to premature atherothrombosis. However, when considering the clinical utility of screening for any new marker for cardiovascular disease, physicians should consider whether there is a standardized and reproducible assay for the marker of interest; whether there is a consistent series of prospective epidemiologic studies indicating that baseline elevations of the novel marker predict future risk; and whether assessment of the novel marker adds to the predictive value of other plasma-based risk factors, specifically, the ratio of total cholesterol to high-density lipoprotein cholesterol. In this article, these criteria are used to evaluate five promising markers of cardiovascular risk: lipoprotein(a), total plasma homocysteine, fibrinolytic capacity, fibrinogen, and high-sensitivity C-reactive protein. Background is also provided to assist physicians in deciding whether one or more of these novel markers deserve clinical consideration in general outpatient settings.


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Figure 1.
Relative risk for future myocardial infarction on the basis of simultaneous assessment of high-sensitivity C-reactive protein and the lipid profile.HDL[49]

Data are stratified into low, middle, and high tertiles for both high-sensitivity C-reactive protein and the ratio of total cholesterol to high-density lipoprotein ( ) cholesterol. From Ridker and colleagues .

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Figure 2.
Relative risk for future myocardial infarction among apparently healthy middle-aged men in the Physicians' Health Study according to baseline levels of lipoprotein(a), total plasma homocysteine, total cholesterol (TC), fibrinogen, tissue-type plasminogen activator (tPA) antigen, the ratio of total cholesterol to high-density lipoprotein cholesterol (HDLC), and high-sensitivity C-reactive protein (hs-CRP).

For consistency, risks are computed for men in the top compared with the bottom quartile for each marker.

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