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Intraindividual variability of fibrinogen levels and cardiovascular risk profile
R S Rosenson1, C C Tangney, J M Hafner
1Department of Medicine, Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill 60612.
Insights
Fibrinogen levels show significant variability, requiring multiple measurements for accurate cardiovascular risk assessment. A single fibrinogen test may not reliably predict ischemic heart disease or stroke risk.
Area of Science:
- Cardiovascular Science
- Clinical Chemistry
- Biostatistics
Background:
- Prospective studies identify fibrinogen as an independent predictor of ischemic heart disease and stroke.
- Recommendations suggest including fibrinogen in cardiovascular risk profiles.
- Widespread screening necessitates understanding fibrinogen measurement validity.
Purpose of the Study:
- To quantify methodological and intraindividual variability in fibrinogen measurements using the Clauss method.
- To assess the utility of single fibrinogen measurements for risk stratification and reproducibility.
- To determine the impact of fibrinogen variability on sample size calculations.
Main Methods:
- Fibrinogen levels measured via a modified Clauss method.
- Three cohorts of healthy, nonsmoking volunteers studied.
- Intraindividual variability assessed over single-day, 5-day, and 6-week periods.
Main Results:
- Methodological variability (coefficient of variation) was 5.8%.
- Single-day intraindividual variability was 10.7%, increasing to 17.8% over 6 weeks.
- An average of four fibrinogen measures are needed to achieve <10% misclassification error.
Conclusions:
- Significant intraindividual fibrinogen variability impacts its reliability as a single risk marker.
- Multiple fibrinogen measurements are necessary for accurate cardiovascular risk stratification.
- Variability data are crucial for appropriate sample size estimation in clinical studies.
Abstract:
Prospective population studies have established that fibrinogen is an independent predictor for ischemic heart disease and stroke. These study conclusions have prompted recommendations that fibrinogen determinations be included in the cardiovascular risk profile. The routine availability of fibrinogen measurements may result in widespread screening prior to establishing the validity of a single fibrinogen level as an accurate descriptor for individual subjects. The objectives of this study were to describe the methodological and intraindividual components of variability in fibrinogen measurements determined by using the Clauss method; to establish the usefulness of a single fibrinogen measurement on risk stratification and retest reproducibility; and to determine the influence of intraindividual fibrinogen variability on sample size estimates. Fibrinogen levels were measured by a modification of the Clauss method. Three cohorts of apparently healthy, nonsmoking volunteers were recruited. The single-day intra-individual component of fibrinogen variability was determined in 39 subjects. For the 5-day intraindividual component of fibrinogen variability, 32 subjects were recruited, and in the 6-week intraindividual study, 28 subjects were included. The coefficient of variation for the methodological component of fibrinogen variability was 5.8% as determined from batch analyses, but the intraindividual coefficient of variation for replicate measures on a single day was 10.7%. The 5-day intraindividual coefficient of variation was 14.2%, and for the 6-week period it was 17.8%. Based on the 6-week data, an average of four fibrinogen measures is required to reduce misclassification error to less than 10%. Sample size estimates were made based on predetermined levels of statistical power and the 6-week intraindividual and interindividual variability estimates.(ABSTRACT TRUNCATED AT 250 WORDS)