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


CONCLUSIONS
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.
Pereira
Mark A
MA
University of Minnesota, School of Public Health, Division of Epidemiology, Minneapolis, MN 55454, USA. pereira@epiumn.umn.edu
Weggemans
Rianne M
RM
Jacobs
David R
DR
Hannan
Peter J
PJ
Zock
Peter L
PL
Ordovas
Jose M
JM
Katan
Martijn B
MB
D000328:Adult; D000704:Analysis of Variance; D002784:Cholesterol / Q000097:blood* / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D004032:Diet / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009426:Netherlands; D018962:Phlebotomy / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics; D012737:Sex Factors
D008076:Cholesterol, HDL; D002784:Cholesterol