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6. Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study

Author

Øyri, L. K. (Linn K. L.), Christensen, J. J. (Jacob J.), Sebert, S. (Sylvain), Thoresen, M. (Magne), Michelsen, T. M. (Trond M.), Ulven, S. M. (Stine M.), Brekke, H. K. (Hilde K.), Retterstøl, K. (Kjetil), Brantsæter, A. L. (Anne Lise), Magnus, P. (Per), Bogsrud, M. P. (Martin P.), Holven, K. B. (Kirsten B.), Øyri, L. K. (Linn K. L.), Christensen, J. J. (Jacob J.), Sebert, S. (Sylvain), Thoresen, M. (Magne), Michelsen, T. M. (Trond M.), Ulven, S. M. (Stine M.), Brekke, H. K. (Hilde K.), Retterstøl, K. (Kjetil), Brantsæter, A. L. (Anne Lise), Magnus, P. (Per), Bogsrud, M. P. (Martin P.), and Holven, K. B. (Kirsten B.)

Abstract

Background: Numerous intrauterine factors may affect the offspring’s growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent. Methods: This parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age). Results: Higher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ Pinteraction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ Pinteraction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ Pinteraction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ Pinteraction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ Pinteraction ≤ 0.99). Conclusions: Maternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.

Published
2023

7. LDL cholesterol targets rarely achieved in familial hypercholesterolemia patients:A sex and gender-specific analysis

Author

Schreuder, M. M., Hamkour, S., Siegers, K. E., Holven, K. B., Johansen, A. K., van de Ree, M. A., Imholz, B., Boersma, E., Louters, L., Bogsrud, M. P., Retterstøl, K., Visseren, F. L.J., Roeters van Lennep, J. E., Koopal, C., Schreuder, M. M., Hamkour, S., Siegers, K. E., Holven, K. B., Johansen, A. K., van de Ree, M. A., Imholz, B., Boersma, E., Louters, L., Bogsrud, M. P., Retterstøl, K., Visseren, F. L.J., Roeters van Lennep, J. E., and Koopal, C.

Abstract

Background and aims: Despite lipid lowering therapy (LLT), reaching LDL-C targets in patients with familial hypercholesterolemia (FH) remains challenging. Our aim was to determine attainment of LDL-C target levels and reasons for not reaching these in female and male FH patients. Methods: We performed a cross-sectional study of heterozygous FH patients in five hospitals in the Netherlands and Norway. Clinical characteristics and information about LLT, lipid levels and reasons for not being on LDL-C treatment target were retrospectively collected from electronic medical records. Results: We studied 3178 FH patients (53.9% women), median age 48.0 (IQR 34.0–59.9) years. Median LDL-C before treatment and on-treatment was higher in women compared to men (6.2 (IQR 5.1–7.3) and 6.0 (IQR 4.9–7.2) mmol/l (p=0.005) and 3.0 (IQR 2.4–3.8) and 2.8 (IQR 2.3–3.5) mmol/L (p<0.001)), respectively. A minority of women (26.9%) and men (28.9%) reached LDL-C target. In patients with CVD, 17.2% of women and 25.8% of men reached LDL-C target. Women received less often high-intensity statins and ezetimibe. Most common reported reasons for not achieving the LDL-C target were insufficient effect of maximum LLT (women 17.3%, men 24.3%) and side effects (women 15.2%, men 8.6%). Conclusions: In routine practice, only a minority of women and men with FH achieved their LDL-C treatment target. Extra efforts have to be made to provide FH patients with reliable information on the safety of statins and their long-term effects on CVD risk reduction. If statin treatment is insufficient, alternative lipid lowering therapies such as ezetimibe or PCSK9-inhibitors should be considered.

Published
2023

8. LDL cholesterol targets rarely achieved in familial hypercholesterolemia patients: A sex and gender-specific analysis

Author

Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Interne Geneeskunde Vasculaire, Circulatory Health, Unit Opleiding Aios, Schreuder, M. M., Hamkour, S., Siegers, K. E., Holven, K. B., Johansen, A. K., van de Ree, M. A., Imholz, B., Boersma, E., Louters, L., Bogsrud, M. P., Retterstøl, K., Visseren, F. L.J., Roeters van Lennep, J. E., Koopal, C., Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Interne Geneeskunde Vasculaire, Circulatory Health, Unit Opleiding Aios, Schreuder, M. M., Hamkour, S., Siegers, K. E., Holven, K. B., Johansen, A. K., van de Ree, M. A., Imholz, B., Boersma, E., Louters, L., Bogsrud, M. P., Retterstøl, K., Visseren, F. L.J., Roeters van Lennep, J. E., and Koopal, C.

Published
2023

16. Children with familial hypercholesterolemia display changes in LDL and HDL function: A Cross-sectional study

Author

Christensen, J.J., primary, Narverud, I., additional, Ruuth, M., additional, Heier, M., additional, Jauhiainen, M., additional, Ulven, S.M., additional, Bogsrud, M.P., additional, Kovanen, P.T., additional, Halvorsen, B., additional, Oda, M., additional, Wium, C., additional, Retterstøl, K., additional, Öörni, K., additional, and Holven, K.B., additional

Published
2021
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18. Subjects with familial hypercholesterolemia have lower aortic valve area and higher levels of inflammatory biomarkers

Author

Hovland, A, Narverud, I, Lie Øyri, LK, Bogsrud, MP, Aagnes, I, Ueland, T, Mulder, Monique, Leijten, Frank, Langslet, G, Wium, C, Svilaas, A, Arnesen, KE, Roeters van Lennep, Jeanine, Aukrust, P, Halvorsen, B, Retterstøl, K, Holven, KB, Hovland, A, Narverud, I, Lie Øyri, LK, Bogsrud, MP, Aagnes, I, Ueland, T, Mulder, Monique, Leijten, Frank, Langslet, G, Wium, C, Svilaas, A, Arnesen, KE, Roeters van Lennep, Jeanine, Aukrust, P, Halvorsen, B, Retterstøl, K, and Holven, KB

Abstract

Background: Reduction of the aortic valve area (AVA) may lead to aortic valve stenosis with considerable impact on morbidity and mortality if not identified and treated. Lipoprotein (a) [Lp(a)] and also inflammatory biomarkers, including platelet derived biomarkers, have been considered risk factor for aortic stenosis; however, the association between Lp(a), inflammatory biomarkers and AVA among patients with familial hypercholesterolemia (FH) is not clear. Objective: We aimed to investigate the relation between concentration of Lp(a), measurements of the aortic valve including velocities and valve area and circulating inflammatory biomarkers in adult FH subjects and controls. Methods: In this cross-sectional study aortic valve measures were examined by cardiac ultrasound and inflammatory markers were analyzed in non-fasting blood samples. The study participants were 64 FH subjects with high (n = 29) or low (n = 35) Lp(a), and 14 healthy controls. Results: Aortic valve peak velocity was higher (p = 0.02), and AVA was lower (p = 0.04) in the FH patients compared to controls; however, when performing multivariable linear regression, there were no significant differences. Furthermore, there were no significant differences between the high and low FH Lp(a) groups regarding the aortic valve. FH subjects had higher levels of platelet-derived markers CD40L, PF4, NAP2 and RANTES compared to controls (0.003 ≤ P ≤ 0.03). This result persisted after multiple linear regression. Conclusions: Middle-aged, intensively treated FH subjects have higher aortic valve velocity, lower AVA, and higher levels of the platelet-derived markers CD40L, PF4, NAP2 and RANTES compared to healthy control subjects. The aortic valve findings were not significant after multiple linear regression, whereas the higher levels of platelet-derived markers were maintained.

Published
2021

23. Lipoprotein (a) concentration is associated with plasma arachidonic acid in subjects with familial hypercholesterolemia

Author

Narverud, I. (Ingunn), Bogsrud, M.P. (Martin P.), Øril, L.K.L. (Linn K. L.), Ulven, S.M. (Stine), Retterstøl, K. (Kjetil), Ueland, T. (Thor), Mulder, M.T. (Monique), Roeters van Lennep, J.E. (Jeanine), Halvorsen, B. (Bente), Aukrust, P. (Pål), Veierød, M.B. (Marit), Holven, K.B. (Kirsten B.), Narverud, I. (Ingunn), Bogsrud, M.P. (Martin P.), Øril, L.K.L. (Linn K. L.), Ulven, S.M. (Stine), Retterstøl, K. (Kjetil), Ueland, T. (Thor), Mulder, M.T. (Monique), Roeters van Lennep, J.E. (Jeanine), Halvorsen, B. (Bente), Aukrust, P. (Pål), Veierød, M.B. (Marit), and Holven, K.B. (Kirsten B.)

Abstract

Elevated lipoprotein (a) (Lp[a]) is associated with cardiovascular disease (CVD) and is mainly genetically determined. Studies suggest a role of dietary fatty acids (FAs) in the regulation of Lp(a), however, no studies have investigated the association between plasma Lp(a) concentration and omega-6 FAs. We aimed to investigate whether plasma Lp(a) concentration was associated with dietary omega-6 FA intake, and plasma levels of arachidonic acid in subjects with familial hypercholesterolemia (FH). We included FH subjects with (n=68) and without (n=77) elevated Lp(a) defined as ≥75 nmol/L, and healthy subjects (n=14). Total fatty acid profile was analyzed by Gas Chromatography-Flame Ionization Detector analysis, and the daily intake of macronutrients (including the sum of omega-6 FAs: 18:2n-6, 20:2n-6, 20:3n-6 and 20:4n-6) were computed from completed food frequency questionnaires. FH subjects with elevated Lp(a) had higher plasma levels of arachidonic acid (AA) compared to FH subjects without elevated Lp(a) (P=0.03). Furthermore, both FH subjects with and without elevated Lp(a) had higher plasma levels of AA compared to controls (P<0.001). The multivariable analyses showed associations between dietary omega-6 FA intake and plasma levels of AA (P=0.02), and between plasma levels of Lp(a) and AA (P=0.006). Our data suggest a novel link between plasma Lp(a) concentration, dietary omega-6 FAs and plasma AA concentration, which may contribute to explain the small diet-induced increase in Lp(a) levels associated with lifestyle changes. Although the increase may not be clinically relevant, this association may be mechanistically interesting in understanding more of the role and regulation of Lp(a).

Published
2019
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26. Higher Expression Of Genes Related To T- And B-Cell Pathways In Pbmcs From Children With Versus Without Familial Hypercholesterolemia: A Cross-Sectional Study

Author

Narverud, I., primary, Christensen, J.J., additional, Bakke, S.S., additional, Ulven, S.M., additional, Rundblad, A., additional, Aukrust, P., additional, Espevik, T., additional, Bogsrud, M.P., additional, Retterstøl, K., additional, Ueland, T., additional, Halvorsen, B., additional, and Holven, K.B., additional

Published
2019
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27. Profiling of immune-related gene expression in children with familial hypercholesterolaemia.

Author

Narverud, I., Christensen, J. J., Bakke, S. S., Ulven, S. M., Rundblad, A., Aukrust, P., Espevik, T., Bogsrud, M. P., Retterstøl, K., Ueland, T., Halvorsen, B., and Holven, K. B.

Subjects
GENE expression profiling, FAMILIAL hypercholesterolemia, ATHEROSCLEROSIS, B cells, BLOOD cells, T cells, ANTIGEN presentation, COMPARATIVE studies, GENE expression, LOW density lipoproteins, RESEARCH methodology, MEDICAL cooperation, RESEARCH, EVALUATION research
Abstract

Background: Innate and adaptive immune responses are pivotal in atherosclerosis, but their association with early-stage atherosclerosis in humans is incompletely understood. In this regard, untreated children with familial hypercholesterolaemia may serve as a human model to investigate the effect of elevated low-density lipoprotein (LDL)-cholesterol.Objectives: We aimed to study the immunological and inflammatory pathways involved in early atherosclerosis by examining mRNA molecules in peripheral blood mononuclear cells (PBMCs) from children with FH.Methods: We analysed the level of 587 immune-related mRNA molecules using state-of-the-art Nanostring technology in PBMCs from children with (n = 30) and without (n = 21) FH, and from FH children before and after statin therapy (n = 10).Results: 176 genes (30%) were differentially expressed between the FH and healthy children at P < 0.05. Compared to healthy children, the dysregulated pathways in FH children included the following: T cells (18/19); B cells (5/6); tumour necrosis factor super family (TNFSF) (6/8); cell growth, proliferation and differentiation (5/7); interleukins (5/9); toll-like receptors (2/5); apoptosis (3/7) and antigen presentation (1/7), where the ratio denotes higher expressed genes to total number of genes. Statin therapy reversed expression of thirteen of these mRNAs in FH children.Conclusion: FH children display higher PBMC expression of immune-related genes mapped to several pathways, including T and B cells, and TNFSF than healthy children. Our results suggest that LDL-C plays an important role in modulating expression of different immune-related genes, and novel data on the involvement of these pathways in the early atherosclerosis may represent future therapeutic targets for prevention of atherosclerotic progression. [ABSTRACT FROM AUTHOR]

Published
2020
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32. High lipoprotein (A) levels do not exacerbate aortic valve velocity in a group of fh subjects

Author

Narverud, I., primary, Bogsrud, M.P., additional, Hovland, A., additional, Aagnes, I., additional, Langslet, G., additional, Retterstøl, K., additional, Wium, C., additional, Svilaas, A., additional, Arnesen, K.E., additional, Øyri, L.K.L., additional, Aukrust, P., additional, Halvorsen, B., additional, Yndestad, A., additional, Ulven, S.M., additional, and Holven, K.B., additional

Published
2018
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37. PT02.6: Intake of a Protein-Enriched Milk and Effects on Muscle Mass and strength. A 12-week Randomized Placebo Controlled Trial Among Community-Dwelling Elderly

Author

Ottestad, I., primary, Løvstad, A.T., additional, Gjevestad, G.O., additional, Hamarsland, H., additional, Saltytè Benth, J., additional, Andersen, L.F., additional, Bye, A., additional, Biong, A.S., additional, Retterstøl, K., additional, Iversen, P.O., additional, Raastad, T., additional, Ulven, S.M., additional, and Holven, K.B., additional

Published
2016
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42. Intake of a protein-enriched milk and effects on muscle mass and strength. A 12-week randomized placebo controlled trial among community-dwelling older adults.

Author

Gjevestad, G., Šaltytė Benth, J., Bye, A., Iversen, P., Ulven, S., Holven, K., Ottestad, Inger, Andersen, L., Retterstøl, K., Løvstad, A., Hamarsland, H., Raastad, T., and Biong, A.

Subjects
BLOOD collection, BODY composition, STATISTICAL correlation, DIETARY supplements, EXERCISE tests, GRIP strength, INTERVIEWING, LIFE skills, MILK proteins, MUSCLE contraction, MUSCLE strength, NONPARAMETRIC statistics, STATISTICAL sampling, STATISTICS, T-test (Statistics), DATA analysis, RANDOMIZED controlled trials, TREATMENT effectiveness, INDEPENDENT living, STAIR climbing, BLIND experiment, DATA analysis software, DESCRIPTIVE statistics, PHOTON absorptiometry, OLD age
Abstract

Objectives: To investigate the effect of 20 g protein with breakfast and evening meal on muscle mass, muscle strength and functional performance in older adults. Design: A double-blinded randomized controlled study. Setting: Oslo and Akershus University College of Applied Sciences, Norway. Participants: Healthy community-dwelling men and women (≥ 70 years) with reduced physical strength and/or performance. Intervention: Subjects were randomly assigned to receive either protein-enriched milk (2 x 0.4 L/d; protein group) or an isocaloric carbohydrate drink (2 x 0.4 L/d; control group) with breakfast and evening meal for 12 weeks. Measurements: The primary endpoints were muscle mass measured by dual X-ray absorptiometry, and tests of muscle strength (one repetition maximum test of chest press and leg press) and functional performance (handgrip strength, stair climb and repeated chair rise). Results: In total, 438 subjects were screened, 50 subjects were randomized and 36 completed the study. Chest press improved significantly in the protein (1.3 kg (0.1-2.5), p=0.03) and the control group (1.5 kg (0.0-3.0), p=0.048), but with no difference between the groups (p=0.85). No significant change in leg press (p=0.93) or muscle mass (p=0.54) were observed between the protein and the control group. Nor did we observe any significant differences in the functional performance tests (p>0.05 for all tests) between the groups. Conclusion: Increased protein intake (2 x 20 g/d) did not significantly improve muscle mass, muscle strength or functional performance in healthy older weight stable adults. Whether intake of > 20 g protein to each meal is necessary for preservation of muscle mass and strength in older adults should be further investigated in a larger study. This underscores the need for well-designed studies that can differentiate between the effect of protein intake and increased energy. This trial was registered at Clinicaltrials.gov (ID no. NCT02218333). [ABSTRACT FROM AUTHOR]

Published
2017
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44. Oxidized LDL level is related to gene expression of tumour necrosis factor super family members in children and young adults with familial hypercholesterolaemia

Author

Narverud, I., primary, Halvorsen, B., additional, Nenseter, M. S., additional, Retterstøl, K., additional, Yndestad, A., additional, Dahl, T. B., additional, Ulven, S. M., additional, Olstad, O. K., additional, Ose, L., additional, Holven, K. B., additional, and Aukrust, P., additional

Published
2012
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