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Title: WITHIN-PERSON VARIATION IN SERUM LIPIDS: IMPLICATIONS FOR CLINICAL TRIALS

Author
item PEREIRA, MARK - UNIV OF MINNESOTA
item WEGGEMANS, RIANNE - UNILEVER HEALTH INSTITUTE
item JACOBS, DAVID - UNIV OF MINNESOTA
item HANNAN, PETER - UNIV OF MINNESOTA
item ZOCK, PETER - WAGENINGEN UNIVERSITY
item ORDOVAS, JOSE - TUFTS-HNRCA
item KATAN, MARTIJN - WAGENINGEN UNIVERSITY

Submitted to: International Journal of Epidemiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/22/2003
Publication Date: 3/1/2004
Citation: PEREIRA, M.A., WEGGEMANS, R.M., JACOBS, D.R., HANNAN, P.J., ZOCK, P.L., ORDOVAS, J.M., KATAN, M.B. WITHIN-PERSON VARIATION IN SERUM LIPIDS: IMPLICATIONS FOR CLINICAL TRIALS. INTERNATIONAL JOURNAL OF EPIDEMIOLOGY. 2004;33:1-8.

Interpretive Summary: Blood cholesterol levels are recognized as a major risk factor for cardiovascular disease; however, we have much to learn about the degree to which behavioral, biological, and genetic factors contribute to its variability within the individual. In this research, we have examined within-person variation in blood cholesterol and in high-density lipoprotein (HDL) cholesterol in about 500 subjects who participated in 27 dietary intervention studies from 1976 to 1995. We found significant evidence supporting the contribution of genetic factors involved in lipoprotein metabolism. Moreover, our analyses uncovered a number of factors and participant characteristics, which result in augmented within-person lipid variance, and results in increased in sample size requirements. Our findings will have important implications for the time and cost of such nutritional interventions.

Technical Abstract: Little is known about the degree to which behavioral, biological, and genetic traits contribute to within-person variation in serum cholesterol. The authors studies 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. 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) polymorphism may increase the within-person variation in total cholesterol. 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 be important implications for the time and cost of such interventions.