Update on Selected Markers Used in Risk Assessment for Vascular Disease

Clinical Laboratory Science, Winter 2004 by Carreiro-Lewandowski, Eileen

While hs-CRP may serve as a useful predictor of increased CHD, widespread screening of the adult population as a public health measure is not recommended at this time.3,13 Guidelines for hs-CRP utilization published by the CDC/American Heart Association indicate that results should be uniformly expressed in units of mg/L.14 Using standardized assays, cutpoints of low risk (3.0 mg/L) correspond to tertiles based on population distributions (40,000 individuals) of hs-CRP when reviewed by this working group. Based on these findings, coupled with other recent scientific studies, this same group recommended that hs-CRP serve as the representative atherosclerotic inflammatory marker, but only in certain circumstances. Risk assignment should only occur in those individuals free from other inflammatory conditions, in those patients with an intermediate 10-year CHD risk (10% to 20% Framingham Risk Score/ATP III guidelines), in the absence of other major risk factors including known CHD, or at the discretion of the physician, particularly in those patients having baseline risk but for whom further guidance is needed when establishing risk assessment or a treatment plan. The assay may be useful as an independent marker in patients with stable coronary disease, stroke, peripheral artery disease, acute coronary syndromes, or for assessing the likelihood of recurrent events, such as restenosis or death.15

In addition to the presence of inflammatory disease, hs-CRP has several limitations. Little data exists for racial and ethnic populations. The use of estrogen in hormone replacement therapy (HRT) is associated with increased hs-CRP levels and LDL levels, however, the link of HRT and increased hs-CRP to increase CHD risk or incidence has not been established.16 Increased body weight, body mass index, elevated blood pressure, cigarette smoking, low HDL/high triglycerides, and the metabolic syndrome are associated with increased hs-CRP, while weight loss, moderate alcohol consumption, and increased physical activity, particularly endurance exercise, reduces hs-CRP levels. The mechanisms are poorly defined, but these associations bring into question the role of insulin-resistance and its relationship to hsCRP and its contribution to CHD.

Promising data exists for increased hs-CRP as a significant risk factor when used in combination with the HDL/total cholesterol in women with values within suggested guidelines.l7 In a more recent study reported by Ridker, hs-CRP and LDL cholesterol (direct-measurement assay) were measured in all of the participants in the Women's Health Study (27,939 women over 45 years of age).18 Their data suggests that hs-CRP may be superior to LDL in predicting the risk of first cardiovascular events, including stroke, nonfatal myocardial infarction, coronary revascularization procedures, and death from cardiovascular causes in this population even after other risk factors, including HRT, were accounted for in the results. Seventy-seven percent of first cardiovascular events in the study occurred in those with LDL levels below 160 mg/dL, and 46% occurred in those with levels below 130 mg/dL.