Within-person variation in serum lipids: implications for clinical trials

Int J Epidemiol. 2004 Jun;33(3):534-41. doi: 10.1093/ije/dyh057. Epub 2004 Mar 11.

Abstract

Background: Little is known about the degree to which behavioural, biological, and genetic traits contribute to within-person variation in serum cholesterol. Materials and Methods The authors studied within-person variation in serum total and high density lipoprotein (HDL) cholesterol in 458 participants of 27 dietary intervention studies in Wageningen, The Netherlands, from 1976 to 1995.

Results: For a median of 4 days between blood draws, the geometric mean of the within-person standard deviation was 0.13 mmol/l ( approximately 5 mg/dl, coefficient of variation = 3.0%) for total cholesterol and 0.04 mmol/l ( approximately 1.5 mg/dl, coefficient of variation = 3.0%) for HDL cholesterol. In mixed-model linear regressions using within-person variance as the dependent variable and including lipid concentration and covariates listed below, within-person variance of both total cholesterol and HDL cholesterol was higher for greater number of days between blood draws and for self-selected diet rather than investigator-controlled diet. Within-person variance of total cholesterol only was higher for non-standardized versus standardized phlebotomy protocol and for female sex. The authors found evidence that the APOA4 -347 (12/22 genotype) and MTP -493 (11 genotype) polymorphisms may increase the within-person variation in total cholesterol.

Conclusion: Under certain study design (self-selected diet, use of non-standardized phlebotomy protocol) or participant characteristics (female, certain polymorphisms) within-person lipid variance is increased and required sample size will be greater. These findings may have important implications for the time and cost of such interventions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analysis of Variance
  • Cholesterol / blood*
  • Cholesterol / genetics
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / genetics
  • Diet / methods
  • Female
  • Genotype
  • Humans
  • Male
  • Netherlands
  • Phlebotomy / methods
  • Polymorphism, Genetic / genetics
  • Sex Factors

Substances

  • Cholesterol, HDL
  • Cholesterol