Should CRP Testing be Routine?

Summarized by Robert W. Griffith, MD
November 28, 2002 (Reviewed: November 13, 2004)

Introduction

Everyone's been told that they should watch their low-density lipoprotein (LDL) cholesterol level, and, if it's raised, take action. It's a major risk factor for cardiovascular disease (CVD), and lowering it, using lifestyle changes and medications, helps reduce heart attacks. New, lower, target levels for LDL-cholesterol levels have been issued, to try to improve outcomes still further; we summarized these recently (see first link below).

However, some people get coronary artery disease without having raised LDL levels. As some types of inflammation have been shown to cause arterial changes, interest has increased in measuring C-reactive protein (CRP), an indicator of inflammation in the body, as a possible predictor of CVD. Now a 'head-to-head' study of the predictive values of these two tests has been reported in the New England Journal of Medicine.

How the study was done

Between 1992 and 1995 scientists measured CRP and LDL-cholesterol levels in 28,000 participants in the US Women's Health Study. They also collected information on lifestyle factors at that time. The women were carefully followed for an average of 8 years, with any cardiovascular 'events' during that time (e.g. heart attack, stroke, bypass surgery, sudden heart death) recorded.

All the women were classified into one of five equally sized groups based on their CRP levels, and again using their LDL-cholesterol levels. Such groupings are called 'quintiles'. Analyses of the likelihood of having a cardiovascular event were calculated for each quintile, comparing the chances with the lowest-level quintiles for CRP and LDL-cholesterol, respectively. Adjustments were made for age, use of hormone replacement therapy, cigarette smoking, raised blood pressure, the presence of diabetes, and high-density lipoprotein ('good') cholesterol levels.

What was found

At the start of the study, the average age of the women was 55. Less than half (44%) were on hormone replacement therapy, 25% had high blood pressure, 12% smoked, and 2.5% had diabetes. Their average CRP was 1.6 mg/L, and average LDL-cholesterol 124 mg/dL (3.2 mmol/L).

The likelihood of their having a first cardiac event for the different quintiles of CRP and LDL cholesterol are shown in the tables, with the lowest quintiles for each set at 1.0:

C-reactive Protein

LDL Cholesterol

It can be seen that high levels of CRP were more likely to be associated with an adverse cardiovascular event than high levels of LDL cholesterol. Put another way, CRP levels seem to offer better prediction of cardiovascular events than LDL cholesterol levels. This was confirmed by another analysis of the data.

The study also backed up an earlier finding - nearly half of the cardiovascular events (46%) occurred in women who had LDL cholesterol levels below 130 mg/dL (3.36 mmol/L), i.e. in women who didn't have clearly raised LDL levels.

What does this mean?

So, should CRP determinations replace LDL-cholesterol levels as routine test for increased cardiovascular risk? The answer is "no". LDL-cholesterol levels have an enormous track record of predictability, and treating them (with lifestyle changes and medications) has been shown in numerous studies to result in lessened heart attacks, strokes, and cardiac deaths. We don't have this sort of information for CRP levels.

Nevertheless, there's no doubt that something must be done for those people who don't have raised cholesterol levels but are possibly still at increased cardiovascular risk. So although it would be wrong to replace LDL cholesterol determinations with CRP levels, there are good arguments for adding CRP tests to routine cardiovascular screens.

It is probably not 'good practice' to try to lower CRP levels with a course of antibiotics; however, increased values may serve as a warning to people that their lifestyle requires some modification. Elevated CRP levels are lowered by both exercise and statin drugs, both of which are beneficial in people with raised cholesterol levels.

Source

• Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. PM. Ridker, N. Rifai, L. Rose,  et al., N Engl J Med, 2002, vol. 347, pp. 1557--1565

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