everal years ago there arrived at the offices of The Lancet a sample of a device consisting of superimposed rotatable discs. This was intended to allow estimation of an individual’s risk of cardiovascular disease. Pessimists about this approach to preventive medicine observe that two powerful risk factors are your age and family history, neither being amenable to change. Also there is a strong residual risk, summing elements as yet unknown or even, perhaps, unknowable; on one estimate, 20-30% of all heart attacks and strokes happen in people without major risk factors. On the other hand, epidemiologic studies have shown up habits and measurements such as smoking and diet and high blood pressure and raised cholesterol that can be altered by drugs and/or changes in lifestyle. The search goes on, and a candidate currently attracting much attention is C-reactive protein, or CRP (paper # 1 and #6).

Dr. Paul M. Ridker’s group, based in Boston, Massachusetts, had shown back in 1997 that CRP was in men a predictor of cardiovascular disease. Paper #6 confirms this finding for women. Combined with lipid measurements it was more powerful than lipid alone. "Moreover, and very exciting we think… the CRP response predicts risk even when lipid levels are low," Ridker tells Science Watch.

CRP is an acute-phase reactant—that is, it rises when there is inflammation or infection. This does not mean the protein is itself causing the disease, and physicians would be reluctant to "treat" a raised CRP as such. But if abnormally high concentrations of CRP in the circulation can be lowered, that would be a step in the right direction; and if the agent capable of achieving this already had an established niche in the cardiovascular field, so much the better.

Drugs in the class known as "statins" affect lipid concentrations by inhibiting a key step in the cholesterol synthesis pathway, but for some time now there have been hints at other actions. Paper #6 may be in part confirmatory but the other Ridker entrant, coming straight in at #1, looks more innovative. Statins (here pravastatin) seem to reduce CRP levels in a way that is independent of lipid; "We are coming much closer to accepting the notion that statins are also anti-inflammatory drugs," Ridker adds.

The main result of the CARE (Cholesterol And Recurrent Events) secondary prevention trial was published five years ago. Pravastatin lowered by about a quarter the rate of fatal and non-fatal heart attacks in patients who had survived one previously. Paper #1 reports that CRP levels tended to rise in the placebo group from this trial and fall, by about one-fifth, in the pravastatin group, independently of baseline lipid levels. In an earlier CARE paper, Ridker's group had shown that the reduction in cardiovascular events attributable to the statin was larger if the CRP was raised. In paper #1, to avoid bias, patients were selected from those who had not had a recurrent event in the trial. However, two further papers (they may be out by the time this issue of Science Watch is published) do address directly the question of whether those for whom cholesterol is not a problem but whose CRP is high really do benefit significantly from statin therapy in terms of event reduction.