Once Again, Do You Know Your CRP?

Summarized by Robert W. Griffith, MD
February 11, 2005

Introduction

In September 2002 we posted an article "Do you know your CRP?" Since then, experts have strengthened their opinion that this blood protein, which is a recognized 'marker' for inflammatory processes in the body, is linked to the occurrence of atherosclerosis. Two recent studies published in the New England Journal of Medicine lend considerable support to this theory, equating an elevated level of CRP with a raised blood cholesterol as risk factors for coronary artery disease (CAD). Further, the use of statin drugs (which were originally developed as cholesterol-lowering agents) is linked to reductions in CRP levels along with reduced evidence of atherosclerosis, and fewer heart attacks or deaths in patients who have had a previous attack. We've summarized the initial results from these two studies before (see second link below), so we'll confine ourselves here to the new findings.

The Ridker et al. study

There were 3,745 heart attack or severe coronary angina patients enrolled, who were given either a high dose of a statin (atorvastatin 80 mg daily) or a low dose (pravastatin 40 mg daily). They were classified into 4 equally-sized groups according to their LDL cholesterol levels (quartiles). And then they were allocated to different quartiles with respect to their CRP levels.

Setting the risk of a lethal or non-lethal heart attack as "1" for the lowest LDL quartile, the risks increased for the low-mid, through the high-mid, through the high quartile from 1.1 to 1.2 to 1.7. In other words, those in the high LDL group had 1.7-times the risk of a severe cardiac effect than those with low LDL levels. Using the same procedure for CRP levels, the risks for the 4 quartiles were 1.0 (set), 1.4, 1.3, and 1.7, respectively. Interestingly, LDL and CRP levels did not correlate well in individuals, i.e. someone could be in the high quartile for CRP and the low quartile for LDL cholesterol.

Those patients who had an LDL cholesterol level below 70 mg/dL (1.7 mmol/L) at the end of the study had a risk of 2.7 cardiac events per 100 patient-years, compared with 4.0 events for those with a higher LDL cholesterol. Those with a CRP below 2 mg/L had an 'event risk' of 2.8 per 100 patient-years, versus 3.9 events for CRP levels over 2 mg/L. There was no difference in these results dependant on the type of statin taken.

Both statins lowered LDL and CRP levels, with atorvastatin being more effective (but it was dosed higher). However, any benefit of atorvastatin was confined to its effects on one or other of these two levels.

The Nissen et al. study

In this study over 500 subjects with CAD on angiography were given one of the same statin drugs at the same dosage, for 18 months. At the end of this time, coronary ultrasonography revealed a greater degree of progression of atherosclerosis in the subjects with higher LDL cholesterol and CRP levels. It was clear that more intensive statin therapy (as in the atorvastatin patients) was linked to a greater reduction in the rate of atherosclerosis progression.

What these results mean

An editorial¹ in the same issue of the Journal comments on these results as follows: "If ever there were a perfect marriage of drug with disease it might be between statins and atherosclerosis." Dr Ehrenstein, the editorialist, links the anti-inflammatory action of statins with the known inflammatory component of atherosclerosis; the list of diseases in which statins may be beneficial now include multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosis (SLE). He goes on to speculate on the actual mechanism by which statins could produce this effect, namely by reducing cholesterol levels in the cell membranes at sites of lymphocyte activity (lymphocytes are a type of white blood cells associated with chronic inflammation).

The findings reported in these two studies show the importance of statin therapy in preventing cardiac events, such as heart attack and unstable angina. And statins are probably not the end of the story. Drug companies will certainly work diligently to find other, better, anti-inflammatory drugs that can arrest or reverse the atherosclerotic process. In the meantime we have a small array of safe and effective statins, and we should make good use of them.

Sources

• C-reactive protein levels and outcomes after statin therapy. PM. Ridker, CP. Cannon, D. Morrow,  et al., N Engl J Med, 2005, vol. 352, pp. 20--28





• Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. SE. Nissen, EM. Tuzcu, P. Schoenhagen,  et al., N Engl J Med, 2005, vol. 352, pp. 29--38

Footnotes
1. Statins for atherosclerosis -- as good as it gets? MR. Ehrenstein, EC. Jury, C. Mauri, N Engl J Med, 2005, vol. 352, pp. 73--75

Related Links
Do You Know Your CRP?
Should We Put Statins in the Drinking Water?
Statins Work Even When the Cholesterol Isn't Raised