Ten-year standardization of lipids and high-sensitivity C-reactive protein in a randomized controlled trial to assess the effects of statins on secondary stroke prevention: Japan Statin Treatment Against Recurrent Stroke

Abstract

Background The Japan Statin Treatment Against Recurrent Stroke (J-STARS) is a clinical trial that administered pravastatin for secondary stroke prevention. Lipid concentrations are a well-established risk factor for cerebrovascular diseases. Elevated high-sensitivity C-reactive protein (hs-CRP) indicates a high risk of inflammatory reactions. In clinical trials, internationally approved standardization is essential for obtaining study results that are comparable with those from overseas. Therefore, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and hs-CRP were standardized throughout a 10-year study period. Methods J-STARS specified a single clinical laboratory for blood analyses. Four lipids were evaluated by calculating the total error: accuracy (absolute mean %bias vs. reference value) + precision (1.96 among-run coefficient of variation [CV, %]). Accuracy for hs-CRP was ensured using a calibrator traceable to the international plasma protein reference material and precision was evaluated by CV. Results Average total errors (standard deviation, %) throughout the study period were as follows: TC 1.35% (0.290%), HDL-C 2.45% (1.087%), LDL-C 2.65% (0.956%) and TG 3.70% (0.559%). Four lipids met the performance criteria of the US Centers for Disease Control and Prevention (CDC). The precision of hs-CRP was 3.28% (0.627%), which met the performance criterion established by the American Heart Association/CDC. Conclusions Based on standardization, the results of J-STARS appear to be comparable with those of similar intervention-based clinical studies on statins overseas. These study results will contribute to the establishment of preventive measures against recurrent stroke in Japanese patients. J-STARS is registered in ClinicalTrials.gov under NCT00221104.

Keywords: CDC; CRMLN; J-STARS; hs-CRP; lipids; standardization.