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

Mark A. Pereira, Rianne M. Weggemans, David R. Jacobs, Peter J. Hannan, Peter L. Zock, Jose M. Ordovas, Martijn B. Katan

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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 (∼5 mg/dl, coefficient of variation = 3.0%) for total cholesterol and 0.04 mmol/l (∼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.

Original languageEnglish (US)
Pages (from-to)534-541
Number of pages8
JournalInternational journal of epidemiology
Volume33
Issue number3
DOIs
StatePublished - Jun 2004

Bibliographical note

Funding Information:
The authors appreciate the willingness of the study subjects to donate their DNA for this research. The generosity of the Institute for Anthropogenetics at Leiden University, The Netherlands, in allowing time and space for the genotyping is also greatly appreciated. In addition, the authors thank Juan Pedro-Botet for performing some of the genotyping. This research was funded in part by The Netherlands Heart Foundation, grant number 95.118 (RMW), The Wageningen Centre for Food Sciences (MAP), and Grants T32HL07779 (MAP) and R01HL54776 (JMO) from the National Heart, Lung, and Blood Institute, USA.

Keywords

  • Cholesterol
  • Data interpretation
  • Diet
  • Lipoproteins
  • Periodicity
  • Randomized controlled trials

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