Nutrient intake and blood pressure in the Dietary Intervention Study in Children.

Delineating the role that diet plays in blood pressure levels in children is important for guiding dietary recommendations for the prevention of hypertension. The purpose of this study was to investigate relationships between dietary nutrients and blood pressure in children. Data were analyzed from 662 participants in the Dietary Intervention Study in Children who had elevated low-density lipoprotein cholesterol and were aged 8 to 11 years at baseline. Three 24-hour dietary recalls, systolic pressure, diastolic pressure, height, and weight were obtained at baseline, 1 year, and 3 years. Nutrients analyzed were the micronutrients calcium, magnesium, and potassium; the macronutrients protein, carbohydrates, total fat, saturated fat, polyunsaturated fat, and monounsaturated fat; dietary cholesterol; and total dietary fiber. Baseline and 3-year longitudinal relationships were examined through multivariate models on diastolic and systolic pressures separately, controlling for height, weight, sex, and total caloric intake. The following associations were found in longitudinal analyses: analyzing each nutrient separately, for systolic pressure, inverse associations with calcium (P < .05); magnesium, potassium, and protein (all P < .01); and fiber (P < .05), and direct associations with total fat and monounsaturated fat (both P < .05); for diastolic pressure, inverse associations with calcium (P < .01); magnesium and potassium (both P < .05), protein (P < .01); and carbohydrates and fiber (both P < .05), and direct associations with polyunsaturated fat (P < .01) and monounsaturated fat (P < .05). Analyzing all nutrients simultaneously, for systolic pressure, direct association with total fat (P < .01); for diastolic pressure, inverse associations with calcium (P < .01) and fiber (P < .05), and direct association with total and monounsaturated fats (both P < .05). Results from this sample of children with elevated low-density lipoprotein cholesterol indicate that dietary calcium, fiber, and fat may be important determinants of blood pressure level in children.

Coronary risk factors in adolescents related to their knowledge of familial coronary heart disease and hypercholesterolemia: the Muscatine Study.

OBJECTIVE: To determine the utility of a school-based questionnaire, to identify adolescents with adverse coronary risk factor levels. DESIGN: In Muscatine, IA, students (9th through 12th grade) completed a questionnaire providing medical history information about first- and second-degree relatives. Anthropometric measures were obtained and blood pressure, lipid, lipoprotein, and apolipoprotein levels were determined. RESULTS: A history of parental coronary heart disease (CHD) was rare and a history of parental high cholesterol frequently was unknown; however, when known, a history of high cholesterol or early (30 to 55 years of age) or later (> 55 years of age) CHD (myocardial infarction, coronary bypass, or death from a heart attack) in grandfathers enriched the identification of adolescents with adverse coronary risk factors. Parental history of CHD was associated with an increased risk for high body mass index and low apolipoprotein A1 levels in their children. Grandfather history of early or later CHD was associated with an increased risk for low apolipoprotein A1 and high density lipoprotein cholesterol levels and high body mass index in their grandchildren. Students with positive grandfather histories of high cholesterol had higher total cholesterol, low density lipoprotein cholesterol, apolipoprotein B, and low density lipoprotein cholesterol to high density lipoprotein cholesterol ratios. Grandmother histories, because most were negative, did not help identify adolescents in this population with adverse coronary risk factors. CONCLUSIONS: A parental history of CHD as well as a grandfather history of high cholesterol or CHD enriches the identification of children with adverse coronary risk factor levels. The positive predictive values associated with using a school-based history obtained from adolescents, many with the aid of their parents, are small and many adolescents do not know their family history. It is essential that pediatricians inquire about parental and especially grandparental medical histories in accordance with the National Cholesterol Education Program guidelines to help identify children at highest familial risk. The importance of determining parental and grandparental histories of CHD or hypercholesterolemia should be emphasized to families who are uncertain of their histories to identify children and adolescents who require a physician's care. It is also important for pediatricians to remind their colleagues who care for patients with premature ischemic heart disease to refer their progeny for pediatric care so that their lipids and lipoproteins may be screened and counseling provided.

Low density lipoprotein receptors bind and mediate cellular catabolism of normal very low density lipoproteins in vitro.

Very low density lipoproteins (VLDL) are heterogeneous, triglyceride-rich particles that are precursors of low density lipoproteins (LDL). Before conversion to LDL, the majority of VLDL are irreversibly cleared from plasma by uncertain mechanisms. To investigate one potential mechanism for VLDL clearance, we studied the ability of LDL receptors to mediate VLDL uptake in vitro. Small, intermediate, and large VLDL from normolipidemic humans were found to bind and undergo catabolism via LDL receptors on normal human fibroblasts. Binding to cell surfaces was up-regulated by lovastatin, an inducer of LDL receptors. Both LDL and a monoclonal antibody against the LDL receptor (IgG-C7) prevented binding of 125I-VLDL. Also, VLDL binding to mutant fibroblasts lacking LDL receptors was low. Thus, LDL receptors mediated VLDL interactions with cells. Binding affinity decreased near saturation, and the apparent number of high affinity sites decreased with increasing VLDL particle size. Because LDL receptors are small (M(r) 115,000) relative to VLDL (M(r) 9-24 x 10(6)) and are clustered in clathrin-coated pits, these findings suggest that steric hindrance becomes an important binding determinant near saturation and are consistent with a lattice model for LDL receptor-ligand interactions. The capacity for cellular catabolism of VLDL decreased with increasing particle size, consistent with a lattice model. The lattice model was also supported by differences between 125I-VLDL binding to cell surfaces and binding to partially purified LDL receptors in solid-phase assays in which steric constraints resulting from clustering in clathrin-coated pits are not present. In both cell-surface and solid-phase assays, VLDL bound via apoE, not apoB-100. Our studies establish that normal VLDL interact with LDL receptors and that steric hindrance due to crowding of particles on clustered LDL receptors is an important determinant of their binding and catabolism. These findings suggest that LDL receptors may participate in normal VLDL clearance in vivo.

Lipoprotein lipase induces catabolism of normal triglyceride-rich lipoproteins via the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor in vitro. A process facilitated by cell-surface proteoglycans.

Bovine milk lipoprotein lipase (LPL) induced binding, uptake, and degradation of 125I-labeled normal human triglyceride-rich lipoproteins by cultured mutant fibroblasts lacking LDL receptors. The induction was dose-dependent and occurred whether LPL and 125I-lipoproteins were added to incubation media simultaneously or LPL was allowed to bind to cell surfaces, and unbound LPL was removed by washing prior to the assay. Lipolytic modification of lipoproteins did not appear to be necessary for increased catabolism because the effect of LPL was not prevented by inhibitors of LPL's enzymatic activity, p-nitrophenyl N-dodecylcarbamate or phenylmethylsulfonyl fluoride. However, the effect was abolished by boiling LPL prior to the assay suggesting that major structural features of LPL were required. Also, LPL-induced binding to cells was blocked by an anti-LPL monoclonal antibody but not by antibodies that are known to block apolipoprotein E- or B-100-mediated binding to low density lipoprotein (LDL) receptors. This indicates that LPL itself mediated 125I-lipoprotein binding to cells. Cellular degradation of 125I-lipoproteins was partially or completely blocked by two previously described ligands for the LDL receptor-related protein/alpha 2-macroglobulin receptor (LRP): activated alpha 2-macroglobulin (alpha 2M*), and the 39-kDa receptor-associated protein. These data implicated LRP as mediating LPL-induced lipoprotein degradation and were confirmed by showing that LPL's effects were prevented by an immunoaffinity-isolated polyclonal antibody against LRP. Furthermore, LPL promoted binding of 125I-lipoproteins to highly purified LRP in a solid-phase assay. Heparin or heparinase treatment of cells markedly decreased LPL-induced binding, uptake, and degradation of lipoproteins, but had no effect on catabolism of alpha 2M*. Thus, cell-surface proteoglycans were obligatory participants in the effects of LPL but were not required for LRP-mediated catabolism of alpha 2M*. Taken together, these in vitro findings establish that through interaction with cell-surface proteoglycans, LPL induces catabolism of normal human triglyceride-rich lipoproteins via LRP.