title: Prognostic utility of biochemical markers of cardiovascular risk: impact of biological variability.
abstract: 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 γ' 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. γ' 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 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.
authors: Kristine S
authors: KS
authors: Alexander
authors: Steven C
authors: SC
authors: Kazmierczak
authors: Caryn K
authors: CK
authors: Snyder
authors: Jon A
authors: JA
authors: Oberdorf
authors: David H
authors: DH
authors: Farrell
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis*; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL
references: J Clin Invest. 1993 Apr;91(4):1351-7
references: 8473487
references: Blood. 2009 Nov 12;114(20):4603-4; author reply 4604-5
references: 19965709
references: Circulation. 2010 Feb 23;121(7):948-54
references: 20177011
references: PLoS Med. 2010 Feb 02;7(2):e1000196
references: 20126381
references: Int J Epidemiol. 2009 Feb;38(1):217-31
references: 18930961
references: Thromb Haemost. 2011 Apr;105(4):605-9
references: 21174007
references: Circulation. 2003 Jan 28;107(3):499-511
references: 12551878
references: J Clin Epidemiol. 1997 Apr;50(4):393-9
references: 9179097
references: N Engl J Med. 2012 Oct 4;367(14):1310-20
references: 23034020
references: Thromb Haemost. 2002 Jul;88(1):26-31
references: 12152671
references: Clin Chem. 2001 Mar;47(3):444-50
references: 11238295
references: Ann Clin Biochem. 1993 Jul;30 ( Pt 4):373-6
references: 7691039
references: Am J Epidemiol. 1999 Feb 1;149(3):261-7
references: 9927222
references: Arch Intern Med. 2006 Jul 10;166(13):1368-73
references: 16832001
references: Thromb Res. 2009 May;124(1):121-6
references: 19128820
references: Thromb Res. 2013 Jan;131(1):89-93
references: 23036532
references: Stroke. 2008 Mar;39(3):1033-5
references: 18239174
references: Epidemiology. 2006 Jul;17(4):404-12
references: 16755268
references: J Thromb Haemost. 2009 Dec;7(12):2064-9
references: 19804533
references: Circulation. 2009 May 5;119(17):2408-16
references: 19364974
references: Ann Intern Med. 2012 Mar 20;156(6):438-44
references: 22431676
references: Ann Clin Biochem. 2002 Mar;39(Pt 2):85-8
references: 11928769
references: Arterioscler Thromb Vasc Biol. 2011 Oct;31(10):2345-52
references: 21757653
references: Blood Coagul Fibrinolysis. 2001 Jun;12(4):229-36
references: 11460005
references: J Thromb Haemost. 2007 Apr;5(4):766-73
references: 17263791
references: N Engl J Med. 2006 Dec 21;355(25):2631-9
references: 17182988