Prognostic utility of biochemical markers of cardiovascular risk: impact of biological variability

Abstract

While a variety of biochemical markers are used to help predict the risk of cardiovascular disease, the prognostic utility of any marker used as a risk assessment tool is dependent upon the long- and short-term biologic variability that the marker shows in different individuals. We measured total, LDL and HDL cholesterol, triglycerides, hsCRP, total fibrinogen and γ' fibrinogen in blood samples collected from 15 apparently healthy individuals over the course of one year. Repeated measures variation estimates were used to calculate short- and long-term intraclass correlation coefficients (ICC), within- and between-subject coefficients of variation (CVI and CVG, respectively), validity coefficients and indices of individuality for each marker. HDL cholesterol demonstrated the lowest variability profile, with an ICC of 0.84 and CVI of 11.1 (95% CI: 8.3, 17.0). hsCRP showed the highest levels of short- and long-term within-subject variability (CVI (95% CI): 54.8 (32.8, 196.3) and 77.1 (53.3, 141.3), respectively). Stated differently, it would require five separate measurements of hsCRP, performed on samples collected over multiple days, to provide the risk assessment information provided by a single measurement of HDL cholesterol. γ' fibrinogen demonstrated an ICC of 0.79 and CVI of 14.3 (95% CI: 10.6, 21.9). hsCRP showed very high biological variability, such that a single measurement of hsCRP lacks sufficient clinical utility to justify routine measurement. The variability profile of γ' fibrinogen was not markedly different than HDL cholesterol, necessitating only a limited number of measurements to establish an individual's risk of cardiovascular disease.