Evaluation of C-reactive protein prior to and on-treatment as a predictor of benefit from atorvastatin: observations from the Anglo-Scandinavian Cardiac Outcomes Trial

Sever, P. S., Poulter, N. R., Chang, C. L., Hingorani, A., Thom, S. A., Hughes, A. D., Welsh, P. and Sattar, N. (2012) Evaluation of C-reactive protein prior to and on-treatment as a predictor of benefit from atorvastatin: observations from the Anglo-Scandinavian Cardiac Outcomes Trial. European Heart Journal, 33(4), pp. 486-494. (doi:10.1093/eurheartj/ehr262)

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Publisher's URL: http://dx.doi.org/10.1093/eurheartj/ehr262

Abstract

Aims: We tested whether on-statin C-reactive protein is associated with cardiovascular (CV) outcome in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

Methods and results: ASCOT randomized a subset of 4853 patients with total cholesterol ≤6.5 mmol/L (250 mg/dL) to atorvastatin or placebo. In a case–control study during 5.5-year follow-up, 485 CV cases were age- and sex-matched with 1367 controls. Baseline LDL-cholesterol (LDL-c) and log-transformed C-reactive protein predicted CV events [odds ratio (OR) per 1 standard deviation (SD) 1.31 (95% confidence interval {CI}: 1.10, 1.56), P = 0.002 and OR 1.19 (1.05, 1.34), P = 0.006, respectively]. Including baseline C-reactive protein into a Framingham risk model very modestly improved risk prediction. Baseline C-reactive protein did not indicate the magnitude of the atorvastatin effect on CV outcome (P = 0.54). At 6 months, atorvastatin reduced median LDL-c by 40.3% and median C-reactive protein by 27.4%. In those randomized to atorvastatin, lower on-treatment LDL-c at 6 months was associated with a significant reduction in subsequent CV events [OR 0.41 (0.22, 0.75), P = 0.004] comparing those above and below the median (2.1 mmol/L). In contrast, C-reactive protein below the median (1.83 mg/L) compared with C-reactive protein above the median was not associated with a significant reduction in CV events [OR 0.86 (0.49, 1.51), P = 0.60]. Consequently, addition of on-treatment C-reactive protein to LDL-c did not improve prediction of statin efficacy.

Conclusion: Among these hypertensive patients selected on the basis of traditional CV risk factors, C-reactive protein did not usefully improve the prediction of CV events and, critically, reduction in C-reactive protein associated with statin therapy was not a predictor of CV outcome alone or in combination with LDL-c.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Welsh, Dr Paul and Sattar, Professor Naveed
Authors: Sever, P. S., Poulter, N. R., Chang, C. L., Hingorani, A., Thom, S. A., Hughes, A. D., Welsh, P., and Sattar, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:European Heart Journal
Publisher:Oxford University Press
ISSN:0195-668X
ISSN (Online):1522-9645
Published Online:28 July 2011
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
531741NT-proBNP as a predictor of vascular events in WOSCOPS: using modern epidemiological techniques to test clinical utility of a biomarkerPaul WelshBritish Heart Foundation (BHF)FS/10/005/28147Institute of Cardiovascular and Medical Sciences