Koenig Wolfgang, Sund Malte, Fröhlich Margit, Löwel Hannelore, Hutchinson Winston L, Pepys Mark B
Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Robert-Koch-Strasse 8, D-89081 Ulm, Germany.
Am J Epidemiol. 2003 Aug 15;158(4):357-64. doi: 10.1093/aje/kwg135.
The authors sought to assess the repeatability of measurements of C-reactive protein, an independent predictor of coronary heart disease, in a large cohort of apparently healthy men and to correct earlier estimates of the association of C-reactive protein and coronary heart disease for the measurement error in this protein. They measured C-reactive protein by a high-sensitivity assay in 936 men aged 45-64 years in the MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg cohort in 1984-1985 and remeasured it 3 years later. All men were subjected to an 8-year follow-up of their cardiovascular status. The analytical variation of the assay was small, with the analytical variance component at 1 percent of the within-subject variance component, a repeatability coefficient of 25 percent, and a reliability coefficient of 1.00. In contrast, the within-subject variation of C-reactive protein corresponded to a repeatability coefficient of 740 percent and a reliability coefficient of 0.54, indicating considerable within-subject variation. Based on the authors' estimates, three serial determinations of C-reactive protein should be done to achieve a reliability of 0.75, the value they found for total cholesterol. Correcting the hazard ratios in their original analysis of the association of coronary heart disease and high-sensitivity-assay C-reactive protein for the measurement error in C-reactive protein and covariables leads to a considerably larger estimate. The results suggest that the true association between C-reactive protein and cardiovascular risk is underestimated by a single C-reactive protein determination, and that several serial C-reactive protein measurements should be taken.
作者试图评估C反应蛋白测量的可重复性，C反应蛋白是冠心病的一个独立预测因子，他们在一大群看似健康的男性中进行了评估，并针对该蛋白测量误差校正了C反应蛋白与冠心病关联的早期估计值。他们于1984 - 1985年在奥格斯堡的MONICA（心血管疾病趋势和决定因素监测）队列中，对936名年龄在45 - 64岁的男性进行了高敏检测C反应蛋白，并在3年后重新测量。所有男性都接受了为期8年的心血管状况随访。该检测的分析变异很小，分析方差分量占个体内方差分量的1%，重复性系数为25%，可靠性系数为1.00。相比之下，C反应蛋白的个体内变异对应的重复性系数为740%，可靠性系数为0.54，表明个体内变异相当大。根据作者的估计，应进行三次连续的C反应蛋白测定以达到0.75的可靠性，这是他们在总胆固醇测量中得到的值。针对C反应蛋白和协变量的测量误差，校正他们在冠心病与高敏检测C反应蛋白关联的原始分析中的风险比，会得出一个大得多的估计值。结果表明，单次C反应蛋白测定低估了C反应蛋白与心血管风险之间的真实关联，应该进行多次连续的C反应蛋白测量。
