Comprehensive lipid and metabolite profiling of children with and without familial hypercholesterolemia: A cross-sectional study  Jacob J. Christensen, Stine M. Ulven, Kjetil Retterstøl, Ingunn Narverud, Martin P. Bogsrud, Tore Henriksen, Jens Bollerslev, Bente Halvorsen, Pål Aukrust, Kirsten B. Holven  Atherosclerosis  Volume 266, Pages 48-57 (November 2017) DOI: 10.1016/j.atherosclerosis.2017.09.021 Copyright © 2017 Elsevier B.V. Terms and Conditions

Fig. 1 Lipoprotein particle concentration and metabolic measures in statin treated children with FH (red symbols, n = 17) and non-statin treated children with FH (blue symbols, n = 30), compared with healthy children (black line, n = 57). Estimates on the right side of the zero-line indicate higher level in FH children, whereas estimates on the left side of the zero-line indicate lower level in FH children. Associations (beta coefficients) are log-transformed and SD-scaled, and adjusted for age and gender. Error bars represent 95% confidence intervals (95% CI). The corresponding absolute concentrations in both groups, as well as absolute and log-transformed (relative) differences between groups are shown in Supplemental Table 1, 2 and 3, respectively. Abbreviations (from top left-down, then top right-down): XXL, extremely large; XL, very large; L, large; M, medium; S, small; XS, very small; VLDL, very low-density lipoprotein; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; P, particle concentration; Apo, apolipoprotein; C, cholesterol; Est, esterified; TG, triglycerides; HDL, high-density lipoprotein; D, mean diameter; TotPG, total phosphoglycerides; PC, phosphatidylcholine and other cholines; SM, sphingomyelins; TotCho, total cholines; TG.PG, ratio of TGs to phosphoglycerides; SFA, saturated fatty acids; MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids; FAw6, omega-6 FAs; LA, linoleic acid; FAw3, omega-3 FAs; TotFA, total FAs; UnSat, estimated degree of unsaturation; AcAce, acetoacetate; bOHBut, 3-hydroxybutyrate; Gp, glycoprotein acetyls (mainly a1-acid glycoprotein); Crea, creatinine; Alb, albumin; Ace, acetate; Glc, glucose; Lac, lactate; Cit, citrate; Ala, alanine; Gln, glutamine; Ile, isoleucine; Leu, leucine; Val, valine; Phe, phenylalanine; Tyr, tyrosine; His, histidine. For particles, units are mol/l; for apolipoproteins, units are g/l; for diameter, units are nm; for albumin, unit is signal area; for all other measurements, units are mmol/L. Atherosclerosis 2017 266, 48-57DOI: (10.1016/j.atherosclerosis.2017.09.021) Copyright © 2017 Elsevier B.V. Terms and Conditions

Fig. 2 Lipid content in atherogenic lipoprotein subclasses in statin treated children with FH (red symbols, n = 17) and non-statin treated children with FH (blue symbols, n = 30), compared with healthy children (black line, n = 57). Estimates on the right side of the zero-line indicate higher level in FH children, whereas estimates on the left side of the zero-line indicate lower level in FH children. Associations (beta coefficients) are log-transformed and SD-scaled, and adjusted for age and gender. Error bars represent 95% confidence intervals (95% CI). The corresponding absolute concentrations in both groups, as well as absolute and log-transformed (relative) differences between groups, are shown in Supplemental Table 1, 2 and 3, respectively. Abbreviations (from top left-down, then top right-down): XXL, extremely large; XL, very large; L, large; M, medium; S, small; XS, very small; VLDL, very low-density lipoprotein; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; L, total lipids; P, phospholipids; C, cholesterol; CE, cholesteryl esters; FC, free cholesterol; TG, triglycerides. For all measurements, units are mmol/L. Atherosclerosis 2017 266, 48-57DOI: (10.1016/j.atherosclerosis.2017.09.021) Copyright © 2017 Elsevier B.V. Terms and Conditions

Fig. 3 Lipid content in HDL subclasses in statin treated children with FH (red symbols, n = 17) and non-statin treated children with FH (blue symbols, n = 30), compared with healthy children (black line, n = 57). Estimates on the right side of the zero-line indicate higher level in FH children, whereas estimates on the left side of the zero-line indicate lower level in FH children. Associations (beta coefficients) are log-transformed and SD-scaled, and adjusted for age and gender. Error bars represent 95% confidence intervals (95% CI). The corresponding absolute concentrations in both groups, as well as absolute and log-transformed (relative) differences between groups are shown in Supplemental Table 1, 2 and 3, respectively. Abbreviations (from top left-down, then top right-down): XL, very large; L, large; M, medium; S, small; HDL, high-density lipoprotein; P, particle concentration; L, total lipids; C, cholesterol; CE, cholesteryl esters; FC, free cholesterol; PL, phospholipids; TG, triglycerides. For all measurements, units are mmol/L. Atherosclerosis 2017 266, 48-57DOI: (10.1016/j.atherosclerosis.2017.09.021) Copyright © 2017 Elsevier B.V. Terms and Conditions

Fig. 4 Lipoprotein particle concentration and metabolic measures in healthy children with normal-high LDL-C (red symbols, n = 28), and per 1 mmol/L increments in LDL-C in healthy children (blue symbols, n = 57), compared with healthy children with normal-low LDL-C (black line, n = 29). Estimates on the right side of the zero-line indicate higher level in healthy children with normal-high LDL-C and increments in LDL-C, whereas estimates on the left side of the zero-line indicate lower level in healthy children with normal-high LDL-C and increments in LDL-C. Associations (beta coefficients) are log-transformed and SD-scaled, and adjusted for age and gender. Error bars represent 95% confidence intervals (95% CI). Abbreviations and units as in Fig. 1. Atherosclerosis 2017 266, 48-57DOI: (10.1016/j.atherosclerosis.2017.09.021) Copyright © 2017 Elsevier B.V. Terms and Conditions

Fig. 5 Lipoprotein particle concentration and metabolic measures in non-statin treated FH children, separated by mutation type (red symbols = LDL receptor negative mutations (Null alleles), n = 11; blue symbols = Other mutations, n = 15), compared with healthy children (black line, n = 57). Estimates on the right side of the zero-line indicate higher level in FH children, whereas estimates on the left side of the zero-line indicate lower level in FH. Associations (beta coefficients) are log-transformed and SD-scaled, and adjusted for age only. Error bars represent 95% confidence intervals (95% CI). Abbreviations and units as in Fig. 1. Atherosclerosis 2017 266, 48-57DOI: (10.1016/j.atherosclerosis.2017.09.021) Copyright © 2017 Elsevier B.V. Terms and Conditions

Atherosclerosis 2017 266, 48-57DOI: (10. 1016/j. atherosclerosis. 2017 Copyright © 2017 Elsevier B.V. Terms and Conditions