Statins and C-reactive protein

Abstract

Timo Strandberg and colleagues (Jan 9, p 118)1Strandberg TE Vanhanen H Tikkanen MJ Effect of statins on C-reactive protein in patients with coronary artery disease.Lancet. 1999; 353: 118-119Summary Full Text Full Text PDF PubMed Scopus (195) Google Scholar show that serum C-reactive protein (CRP) concentrations decrease in most cases after treatment with atorvastatin or simvastatin for 4 months in hyperlipidaemic patients with stable coronary artery disease. Since CRP is subject to seasonal fluctuations,2Kwah K-T Woodhouse P Interrelation of vitamin C, infection, haemostatic factors, and cardiovascular disease.BMJ. 1995; 310: 1559-1563Crossref PubMed Scopus (60) Google Scholar there is a risk that such fluctuations may account for the results of this non-controlled study. We undertook studies on the effects of statins in different groups. First, we carried out a randomised study of simvastatin (20 mg daily) in 30 patients, versus acipimox (250 mg thrice daily) in 27 patients for 3 months, in hyperlipidaemic type II diabetic patients (mean age 61 years; 30 men, 27 women). We measured CRP with a sensitive in-house method.3De Maat MPM Haverkate F Kluft C C-reactive protein: a cardiovascular risk factor. Report on the CRP hot-topic workshop Oct 1, 1997.Fibrinolysis Proteolysis. 1998; 12: 323-327Crossref Scopus (15) Google Scholar CRP concentrations at the start of treatment were similar in the two treatment groups and no significant changes were seen after 1·5 months. After 3 months of treatment, CRP concentrations were significantly reduced in the simvastatin group (median change -0·34 mg/L [interquartile range 1·21]; p=0·013), but not in the acipimox group (-0. 06 mg/L [3·61]); in the simvastatin group, CRP concentrations fell in 23 patients and rose in seven patients; in the acipimox group, CRP increased in 14 and decreased in 13. However, the difference in change between the two groups was not significant. The change in CRP did not correlate with changes in total cholesterol, triglyceride, and HDL-cholesterol as a result of treatment. This finding confirms the short-term effect of statins not only for hyperlipidaemic patients with moderately raised CRP (median 1·55 mg/L),2Kwah K-T Woodhouse P Interrelation of vitamin C, infection, haemostatic factors, and cardiovascular disease.BMJ. 1995; 310: 1559-1563Crossref PubMed Scopus (60) Google Scholar but also for hyperlipidaemic type II diabetic patients known to have raised CRP (median 3·16 mg/L [7. 19]),4Kluft C Meijer P Brussaard HE Krane HMJ Schuit AJ Serum neopterin in acute coronary syndromes.Lancet. 1997; 349: 1253Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar and the comparative design argues against seasonal effects. Second, we carried out two studies on the effect of statins on CRP in groups with lower CRP. In a placebocontrolled study in 20 patients with familial hypercholesterolaemia, in which the treatment group received 40 mg pravastatin daily for 9 months, we found no change in CRP from baseline.5De Maat MPM Kluft C Hoogerbrugge N No effect of pravastatin on C-reactive protein and fibrinogen levels.Fibrinolysis Proteolysis. 1999; 13: 29Google Scholar In a study in 45 patients with familial hypercholesterolaemia (mean age 45 years; 21 men, 24 women) who received simvastatin (20 mg daily) for 1 year, median baseline CRP concentrations were 1·21 mg/L [2·47], and CRP concentrations were nonsignificantly reduced after 1 year of treatment (0·97 mg/L [2·13]): CRP concentrations fell in 25 patients, remained the same in one patient, and increased in 19 patients. Taken together, these data suggest that the effects on CRP are independent of lipid effects and occur mainly when the pretreatment value is increased. Further examination showed that the CRP decrements were predominantly present for values above the median in all studies. We propose that CRP reduction of statins is relevant for patients with high concentrations, which is a promising possibility for differential diagnosis and treatment, since it is known that patients with high cholesterol and high CRP have the highest risk of cardiovascular event.