Evaluation of C-Reactive Protein Before and On-Treatment as a Predictor of Benefit of Atorvastatin: A Cohort Analysis From the Anglo-Scandinavian Cardiac Outcomes Trial Lipid Lowering Arm

Study Questions:

Does baseline and/or on-statin C-reactive protein (CRP) predict cardiovascular (CV) outcome beyond low-density lipoprotein cholesterol (LDL-C)?


The relationship of baseline and on-treatment CRP with subsequent CV events was evaluated using Cox models in a subset of white subjects with no history of CV disease from the United Kingdom (ASCOT [Anglo-Scandinavian Cardiac Outcomes Trial]).


During 5.5 years of follow-up, a total of 488 subjects experienced a CV event. CV risk increased with baseline CRP (hazard ratio [HR] per 1 standard deviation: 1.21; 95% confidence interval [CI], 1.09-1.33) in an adjusted model. In the ASCOT Lipid-Lowering Arm, the relative statin effect in preventing CV events did not differ according to tertiles of baseline CRP (p = 0.69). After 6 months of atorvastatin therapy, the median LDL-C and CRP were reduced by 38.7% and 25.8%, respectively. Those who achieved LDL-C below the median had a reduced CV risk (HR, 0.58; 95% CI, 0.34-0.97) compared with those who did not. In contrast, those who achieved a CRP level below the median did not have a reduced risk of CV disease (HR, 0.95; 95% CI, 0.59-1.55). Among those who achieved LDL-C below the median, there was no difference in CV risk whether they also achieved a CRP level below or above the median.


In these primary prevention patients, although baseline CRP independently predicted CV event risk, the achieved CRP level while on statin therapy did not predict CV events, either alone or in combination with LDL-C.


The ASCOT study enrolled patients at high risk for CV events and adds to the literature that there is little evidence for using CRP as an additional predictor of risk beyond that attributable to lipids and the Global Risk Score in persons at intermediate (10-20%) or high risk for CV events who have an indication for statins. In contrast, low-risk patients (6-10%) with an elevated CRP have been shown to have a reduction in CV events on statins, and the benefit correlates with both on-treatment LDL-C and CRP.

Clinical Topics: Dyslipidemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Great Britain, C-Reactive Protein, Biological Markers, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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