Refinement of the association of serum C-reactive protein concentration and coronary heart disease risk by correction for within-subject variation over time
Refinement of the association of serum C-reactive protein concentration and coronary heart disease risk by correction for within-subject variation over time
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DOI：
10.1093/aje/kwg135
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发表时间：
2003-08-15
影响因子：
5
通讯作者：
Pepys, MB
中科院分区：
文献类型：
--
作者：
Koenig, W;Sund, M;Pepys, MB
作者试图评估C反应蛋白（冠心病的一个独立预测因子）测量的可重复性，在一个大型的明显健康男性队列中，并纠正早期对C反应蛋白与冠心病相关性的估计，以纠正该蛋白的测量误差。他们在1984-1985年通过高灵敏度测定法测量了936名年龄在45-64岁之间的男性的C反应蛋白，这些男性在1984-1985年在奥格斯堡队列中监测心血管疾病的趋势和决定因素，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。该测定的分析变异较小，分析方差分量为受试者内方差分量的1%，重复性系数为25%，可靠性系数为1.00。相比之下，C-反应蛋白的受试者内变异对应的重复性系数为740%，可靠性系数为0.54，表明受试者内变异相当大。根据作者的估计，C-反应蛋白的三个系列测定应该完成，以达到0.75的可靠性，他们发现总胆固醇的值。在他们对冠心病和高敏C反应蛋白的关联性的原始分析中，校正C反应蛋白和协变量的测量误差的风险比，导致了相当大的估计。结果表明，C-反应蛋白和心血管风险之间的真正关联被低估了一个单一的C-反应蛋白测定，并应采取几个系列的C-反应蛋白测量。
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.