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.

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.

High-density lipoprotein levels have markedly increased over the past twenty years in Japan.

AIM: The high-density lipoprotein cholesterol(HDL-C) level is a major negative risk factor for atherosclerotic diseases dependent on various lifestyle parameters. Changes in the lifestyle of Japanese individuals over the past several decades is believed to have increased their total cholesterol levels and the incidence of cardiovascular disease in Japan. It is therefore important to assess the long-term trends in the HDL-C levels with respect to public health in the community. METHODS: In this study, accumulated data for the serum/plasma HDL-C levels published in cohort studies and obtained during health checkup programs in Japan were analyzed with respect to timedependent changes. RESULTS: The levels of HDL-C have continuously and significantly increased over the past 20 years by 12-15% according to the National Health and Nutrition Study, other cohort studies and commercially available data. On the other hand, the non-HDL-cholesterol levels demonstrated no changes or only a slight decrease during the same period. This finding is consistent with several sets of data obtained from health checkup programs. The commercially measured levels of serum apoA-I, an independent parameter of serum HDL, also showed a similar long-term increase, supporting the above findings. CONCLUSION: We concluded that the serum/plasma HDL concentrations in Japanese individuals, selectively, have increased continuously and significantly over the past 20 years or more. The reasons for this phenomenon and the consequent public health outcomes have yet to be investigated.