Intrafamilial associations of lipids and lipoproteins in kindreds with hypertriglyceridemic probands: the Princeton School family Study.

Abstract

Using the hypertriglyceridemic recall group of the Princeton School Family Study, the effectiveness and ramifications of family sampling based on hypertriglyceridemic probands were assessed and whether within-family correlations of lipids and lipoproteins outlast the period of shared common household environments were examined. Thirty-two pediatric and 35 adult probands (who had fasting plasma triglyceride in the 95th percentile or above on initial sampling at visit 1) and their 1st-degree relatives were studied; 19 of the 32 pediatric probands (59%) had top quartile triglyceride levels at the Family Study visit, and 14 (44%) were still in the 95th percentile triglyceride level. Twenty of 35 adult probands (57%) retained triglyceride in the 95th percentile or above at the Family Study visit, while 30 (86%) had top-quartile triglyceride levels. Among the 67 probands, more subjects than expected had elevated total and low density lipoprotein (LDL) cholesterol; probands were under- and overrepresented in the top and bottom quartiles, respectively, of the high density lipoprotein (HDL) cholesterol distribution. Twenty-one percent and 12% of the hypertriglyceridemic probands'' siblings and offspring, respectively, also had triglyceride above the age- and sex-specific 95th percentile; siblings'' and offspring''s total and LDL cholesterol were shifted toward higher values. In adult relatives of hypertriglyceridemic probands, a parabolic relationship between triglycerides and LDL cholesterol, positive in the lowest triglyceride tertile and inverse in the top tertile, was observed. This suggests uncoupling of very low density lipoprotein-LDL precursor-product relationships in hypertriglyceridemic subjects. All lipid and lipoprotein correlations were significant for both pediatric and adult siblings. Whatever accounts for significant correlations among siblings for lipids and lipoproteins in hypertriglyceridemic families transends the period of shared common environment. Although environment and heredity in the observed familial trends cannot be differentiated, close sibling and parent-offspring lipid and lipoprotein risk factor associations in hypertriglyceridemic family units suggest sharing of coronary heart disease risk. Presumably, shared genetic and environmental factors that elevate triglyceride, cholesterol and LDL cholesterol and depress HDL cholesterol can be specifically identified, allowing for early intervention.