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

Background: Although 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 on the long- and short-term biological variability that the marker shows in different individuals. Methods: We measured total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol; triglycerides; high-sensitivity C-reactive protein (hsCRP); total fibrinogen; and γ́ fibrinogen in blood samples collected from 15 apparently healthy individuals over the course of 1 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. Results: 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. γ́ Fibrinogen demonstrated an ICC of 0.79 and CVI of 14.3 (95% CI: 10.6, 21.9). Conclusions: 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 γ́ fibrinogen was not markedly different than HDL cholesterol, necessitating only a limited number of measurements to establish an individual's risk of cardiovascular disease.