Kirsten Bjørklund Holven

• Holven, Kirsten Bjørklund; Dahl, Tuva Børresdatter; Bålsrud, Pia; Christensen, Jacob Juel; Ottestad, Inger Olaug & Rundblad, Amanda [Vis alle 15 forfattere av denne artikkelen] (2026). Cetoleic acid rich fish oil increases plasma levels of eicosapentaenoic and docosapentaenoic acids in healthy volunteers: a double-blinded, randomised, controlled trial. British Journal of Nutrition. ISSN 0007-1145. s. 1–28. doi: 10.1017/S0007114526107958. Fulltekst i vitenarkiv Vis sammendrag

  Intake of fish and supplementation with n-3 polyunsaturated fatty acids (PUFA) are associated with reduced incidence of cardiovascular disease (CVD). Cetoleic acid promotes n-3 PUFA generation in salmon and human HepG2 cells, but data in humans are scarce. To explore the effect of cetoleic acid on n-3 PUFA levels, we performed a double-blinded randomised controlled trial in healthy adults (37 females and 12 males) for four weeks. The participants were randomised to consume either capsules with mackerel oil, naturally rich in cetoleic acid, or a control oil, both with a similar concentration of n-3 PUFA. Clinicaltrials.gov (NCT04841044). Supplements with mackerel oil resulted in higher plasma levels of the n-3 PUFAs 20:4n-3 (Eicosatetraenoic acid) and 20:5n-3 (Eicosapentaenoic acid) as compared with those receiving control oil. In addition, those who received the cetoleic-rich capsules had higher levels of 20:4n-3 in the RBC membrane and a decrease in expression of elongation of very long chain fatty acids protein 5 in peripheral blood mononuclear cells. We found no differences in lipid, glucose or C-reactive protein between the two treatment groups, consisting of healthy subjects. Our data suggests that supplementation with cetoleic-rich mackerel oil may result in increased levels of certain n-3 PUFAs. Further studies should include patients with or at risk for metabolic and CVD.

• Langslet, Gisle; Kollstad, Synne; Jørstad, Øystein Kalsnes; Erke, Maja Gran; Retterstøl, Kjetil & Holven, Kirsten Bjørklund (2026). Retinal findings in familial hypercholesterolemia: An exploratory case-control study. Atherosclerosis Plus. ISSN 2667-0909. 65. doi: 10.1016/j.athplu.2026.100571. Fulltekst i vitenarkiv
• Jensen, Silje Marie; Holven, Kirsten Bjørklund; Ulven, Stine Marie; Anfinsen, Åslaug Matre; Dierkes, Jutta & Lysne, Vegard [Vis alle 7 forfattere av denne artikkelen] (2026). Lipoprotein metabolism and inflammation in healthy young subjects – exploring the postprandial and postabsorptive phases following intake of a standardized meal. Atherosclerosis Plus. ISSN 2667-0909. 65. doi: 10.1016/j.athplu.2026.100572. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims: Commonly measured cardiometabolic biomarkers have not been systematically characterized across the long-term continuum of the postprandial and postabsorptive phases. The aim of the present study was to evaluate how the exact time since last meal impacts test results for lipoprotein particles and inflammatory biomarkers. Methods: We used data from a trial where 34 normal-weighted males and females aged 20-30 y were included. Subjects fasted 12 h, had blood sampled at baseline, then consumed a standardized, habitual breakfast meal, and had blood sampled 13 more times over the next 24 h. NMR metabolomics was used to quantify lipoprotein subclasses and various biomarkers, and ELISA to analyze VCAM-1, ICAM-1, E-selectin, and IL-6. We characterized the postprandial and postabsorptive responses using visualizations and non-linear mixed effects models. Results: Six VLDL subclasses increased by 11-429% within 2-4 h postprandially before returning to baseline levels, followed by another increase 8-10 h after intake of the breakfast meal. IDL and three LDL subclasses increased around 10-12% over 24 h. Four HDL subclasses showed an inverse association with VLDL subclasses, reaching their lowest levels about 1 h after the meal and peaking after 8-10 h with a 5-15% increase from baseline. Participants had an average increase of 325% in IL-6 10 h after breakfast, while other inflammatory biomarkers showed little change over time. For most biomarkers, males generally exhibited higher baseline concentrations compared to females, however the responses over time remained similar. Conclusions: Baseline levels and time of return to baseline varied between individuals, with some sex-specific differences in responses. TG-rich lipoproteins and VLDL increased postprandially and normalized by 12-24 h, whereas IDL and LDL showed minor early changes but increased by 24 h. IL-6 increased markedly during the first 10 h and returned to baseline by 12-24 h, while other inflammatory markers changed little.

• Limani, Naman; Henriksen, Hege Berg; Minge, Mina Marie; Sandoval, Viviana; Landberg, Rikard & Lindqvist, Helen M. [Vis alle 9 forfattere av denne artikkelen] (2026). Effect of different sources of saturated and polyunsaturated fatty acids on postprandial inflammation: A double-blind randomized crossover trial. Clinical Nutrition ESPEN. ISSN 2405-4577. 74. doi: 10.1016/j.clnesp.2026.103335. Fulltekst i vitenarkiv
• Ramanathan, Jayanthi; Sullivan, David; Watts, Gerald; Holven, Kirsten Bjørklund & Tiong, Yee Sian (2026). Familial hypercholesterolemia in pregnancy. Current Opinion in Endocrinology, Diabetes and Obesity. ISSN 1752-296X. Publish Ahead of Print. doi: 10.1097/MED.0000000000000954. Fulltekst i vitenarkiv
• Holven, Kirsten Bjørklund; Raal, Frederick J.; Watts, Gerald F.; Christensen, Jacob Juel & Lennep, Jeanine Roeters van (2026). Challenges in the care of woman with familial hypercholesterolaemia during the reproductive period – current evidence and practical guidance. Atherosclerosis. ISSN 0021-9150. 415. doi: 10.1016/j.atherosclerosis.2026.120679. Fulltekst i vitenarkiv
• Bålsrud, Pia; Ulven, Stine Marie; Hjartåker, Anette; Ottestad, Inger Olaug; Retterstøl, Kjetil & Schwab, Ursula [Vis alle 9 forfattere av denne artikkelen] (2026). Association between dietary protein intake and frailty index among home-dwelling older adults; an 8-year follow-up study. The Journal of Nutrition, Health & Aging. ISSN 1279-7707. 30(6). doi: 10.1016/j.jnha.2026.100850. Fulltekst i vitenarkiv
• Klevmoen, Marianne; Lennep, Jeanine Roeters van; Bogsrud, Martin Prøven; Vesterbekkmo, Elisabeth Kleivhaug; Pedersen, Eva Ringdal & Hovland, Anders Wilhelm [Vis alle 14 forfattere av denne artikkelen] (2026). Extensive pregnancy-related off-treatment time in women with familial hypercholesterolaemia. Atherosclerosis. ISSN 0021-9150. 415. doi: 10.1016/j.atherosclerosis.2026.120668. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims: Women with familial hypercholesterolaemia (FH) lose substantial treatment time during their reproductive years as most lipid-lowering therapies are contraindicated from the preconception through the end of breastfeeding. We examined the duration of real-life pregnancy-related off-treatment time in 27 women with FH in Norway. Methods: Women with FH in Norway who had completed the ongoing FH-FEMINA study (ClinicalTrials.gov ID NCT05367310) were included. Women were followed from 36th week of gestation and until one year after delivery or until end of breastfeeding. Information on use of medication before, during and after the current and previous pregnancies was collected. Pregnancy-related off-treatment time was calculated from discontinuation of lipid-lowering therapy when planning pregnancy, throughout pregnancy, and after delivery. Results: The total duration of pregnancy-related off-treatment time after all childbirths (median 1, range 1-3) per woman was a median of 2.9 years (25th-75th percentile; 1.6-4.0), ranging from 0.8 to 12 years. The pregnancy itself accounted for median of 42.1% of the pregnancy-related off-treatment time, whereas the time before and after pregnancy accounted for a median of 57.9% (range 11.4% to 91.2%). When including untreated years in childhood and/or prior to diagnosis, the lifelong off-treatment time represented a median of 66.3% (range 41.9 to 100%) of lifetime without treatment. Conclusion: Early diagnosis and initiation of treatment is essential in girls with FH to compensate for pregnancy-related off-treatment time later in life. To minimize these pregnancy-related off-treatment periods, healthcare professionals should support women with FH to resume lipid-lowering therapy immediately after breastfeeding and between pregnancies. In addition, more knowledge on the potential effects of statin use during pregnancy and breastfeeding on maternal and offspring health is urgently needed.

• Roza, Gia V. Da; Cermakova, Lubomira; Lennep, Jeanine Roeters van; Holven, Kirsten Bjørklund; Iatan, Iulia & Brunham, Liam R. (2025). Lipid changes in females with familial hypercholesterolemia during the menopausal transition period. Atherosclerosis. ISSN 0021-9150. 413. doi: 10.1016/j.atherosclerosis.2025.120587. Fulltekst i vitenarkiv
• Pedersen, Jonas; Hedegaard, Berit Storgaard; Schmidt, Erik Berg; Dahm, Christina C.; Holven, Kirsten Bjørklund & Retterstøl, Kjetil [Vis alle 8 forfattere av denne artikkelen] (2025). Monounsaturated Fatty Acids in Cardiovascular Disease: Intake, Individual Types, and Content in Adipose Tissue as a Biomarker of Endogenous Exposure. Nutrients. 17(15). doi: 10.3390/nu17152509. Fulltekst i vitenarkiv Vis sammendrag

  Unhealthy dietary patterns are a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). International guidelines recommend reducing saturated fatty acid intake while increasing polyunsaturated and monounsaturated fatty acids (MUFAs) to mitigate cardiovascular risk. However, evidence regarding MUFAs and risk of ASCVD remains conflicting, with recent studies raising concern about a potential higher risk associated with MUFA intake. The aim of this narrative review is to provide an overview of current knowledge and gaps in the literature regarding MUFAs and the risk of ASCVD with a focus on intake, individual types, and content in adipose tissue as a biomarker of endogenous exposure. Main findings reveal that most studies have inappropriately combined all MUFAs together, despite individual MUFA types having different biological effects and showing varying correlations between dietary intake and adipose tissue content. Adipose tissue composition may serve as a biomarker of long-term MUFA exposure, reflecting cumulative intake over one to two years while minimizing biases inherent in dietary assessments. However, tissue levels reflect both dietary intake and endogenous synthesis, complicating interpretation. Importantly, the source of MUFAs appears critical, with plant-derived MUFAs potentially offering advantages over animal-derived sources. In conclusion, we suggest that future research should focus on individual MUFA types rather than treating them as a homogeneous group, investigate their specific dietary sources and associations with ASCVD risk, and use adipose tissue biomarkers to improve exposure assessment and clarify causal relationships while considering overall dietary patterns.

• Elshorbagy, Amany; Vallejo-Vaz, Antonio J.; Barkas, Fotios; Lyons, Alexander R.M.; Stevens, Christophe A.T. & Dharmayat, Kanika I. [Vis alle 84 forfattere av denne artikkelen] (2025). Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry. European Heart Journal. ISSN 0195-668X. 46(12), s. 1127–1140. doi: 10.1093/eurheartj/ehae791. Fulltekst i vitenarkiv
• Langslet, Gisle; Asprusten, Emil Andreas; Igland, Jannicke; Holven, Kirsten Bjørklund; Bogsrud, Martin Prøven & Retterstøl, Kjetil (2025). Cardiovascular disease and compliance with lipid-lowering therapy among young individuals with familial hypercholesterolemia in Norway – A register study. American Journal of Preventive Cardiology. 23. doi: 10.1016/j.ajpc.2025.101043. Fulltekst i vitenarkiv Vis sammendrag

  Aims Investigation of cardiovascular disease (CVD), all-cause death and use of statins and ezetimibe among young Norwegian individuals with heterozygous Familial hypercholesterolemia (FH). Methods We included subjects with genetically verified FH born 1988–2008 and twenty controls per FH subject, with linkage to prescription data, hospitalization data and cause of death from national Norwegian health registries. Data on CHD and death during 2008–2018, and for dispensed prescriptions during 2004–2018, were collected. Results 1351 subjects with FH and 27,015 controls were included. Mean age (SD) at start of follow-up was 12.3 (5.4) years. There was one Coronary Heart Disease (CHD) event and 6 deaths in the FH-group and 3 CHD events and 53 deaths in the control group. CHD and all-cause death were non-significantly increased in the FH-group, hazard ratios (95 % confidence intervals) 6.68 (0.69–64.20) and 2.26 (0.98–5.28), respectively. None of the deaths in the FH-group were related to cardiovascular disease. 83 % of subjects with FH had been prescribed a statin, and 21 % ezetimibe. During the first year after the first prescription, 18.5 % of subjects did not refill their prescription within 180 days after the end date of the previous prescription. 69 % and 60 % of subjects with a prescription had >80 % of days covered with statins and ezetimibe, respectively. After 8 years, around 70 % of subjects were covered with statins. Conclusions Results suggest increased risk of CHD in FH relative to controls, but measures are imprecise because of low absolute risks. Compliance with lipid lowering therapy was moderate.

• Dahl, Tuva Børresdatter; Jimenez, Ana Maria Teresa Quiles; Broch, Kaspar; Anstensrud, Anne Kristine; Gullestad, Lars & Andersen, Geir Øystein [Vis alle 16 forfattere av denne artikkelen] (2025). The N-6 methyladenosine dynamics in STEMI and the effect of IL-6 inhibition - a hypothesis generating sub-study of the ASSAIL-MI trial. Frontiers in Immunology. 16. doi: 10.3389/fimmu.2025.1532325. Fulltekst i vitenarkiv Vis sammendrag

  Background: Epitranscriptomics, with m6A as the most prevalent in mammals, is a novel treatment target for inflammatory diseases, including cardiovascular diseases. However, little is known about m6A RNA-regulation during myocardial infarction (MI). Methods: In this explorative sub-study of the ASSAIL-MI trial, we used whole blood samples from patients with acute ST-elevation MI (STEMI) (n=6) at admission and after 3–7 days, and from healthy control subjects (n=3). RNA was isolated, and m6A sites were analyzed using human m6A single nucleotide resolution microarray analysis. mRNA levels were analyzed using RNA sequencing analysis. Results: Compared with controls, patients with STEMI had a strikingly different pattern of m6A deposition. In total, 845 m6A methylation sites in whole blood RNA were hypomethylated and 36 were hypermethylated compared with controls. Of the hypomethylated transcripts, 194 transcripts were lower expressed, while 197 transcripts were higher expressed. The m6A pattern changed from an overall hypomethylation at admission to an overall hypermethylation 3–7 day after admission. Anti-inflammatory treatment with tocilizumab further altered the m6A deposition. Conclusions: In this hypothesis generating study, m6A deposition differs STEMI patients and healthy controls. The m6A pattern changes over the course of 3–7 days. This response is, at least to some degree, is modulated by blocking the IL-6 receptor. Our data may suggest that this post-transcriptional regulation of RNA is involved in the immune response during STEMI, highlighting its potential as a target for therapy in MI.

• Bogsrud, Martin Prøven; Stava, Tonje Talsnes; Berge, Knut Erik; Strøm, Thea Bismo; Retterstøl, Kjetil & Holven, Kirsten Bjørklund (2025). LDL-cholesterol in newborns and children with genetically verified familial hypercholesterolaemia: implications for cholesterol-based screening. European Heart Journal. ISSN 0195-668X. 46(48), s. 5261–5269. doi: 10.1093/eurheartj/ehaf815. Fulltekst i vitenarkiv Vis sammendrag

  Background and Aims: Cholesterol screening in children, with subsequent genetic testing of top percentile, has been suggested as an efficient universal screening approach in familial hypercholesterolaemia (FH). The potential cholesterol-based screening efficacy was investigated in a national genetically based screening programme. Methods: Data were from the Norwegian national family cascade screening programme in FH children from 1998 to 2023. Cholesterol levels [umbilical cord in newborns (n = 113) and venous blood in children 1–12 years old (n = 1346)] in variant positive and variant negative children were compared. Results: LDL cholesterol (LDL-C) was higher in FH newborns vs non-FH newborns [1.22 (.48) vs .68 (.32) mmol/L, P < .001], but overlapped widely. Cut-off levels corresponding to the 95th and 85th percentile would only identify 55.7% and 75.4% of newborns with FH, respectively. Screening efficacy in newborns did not differ in subgroups: boys and girls, null and non-null variants, variant gene, and neither for total cholesterol nor for non-HDL cholesterol. In all other age groups (from 1 to 12 years), LDL-C discriminated highly between mutation FH and non-FH children. Cut-off levels corresponding to 95th and 85th percentile of LDL-C would identify 88.4% and 94.1% of 1–12-year-old children with FH, respectively. Conclusions: Previous studies investigating lipid or genetic screening approaches for FH have limitations of only performing genetic testing in children with high LDL-C levels. The present study is the first to show the true LDL-C overlap in children with FH vs non-FH by utilizing unique data from a national family cascade screening programme. Cholesterol-based screening approaches for FH only seem feasible from 1 year of age onward.

• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Retterstøl, Kjetil & Narverud, Ingunn [Vis alle 10 forfattere av denne artikkelen] (2025). LDL cholesterol burden in elderly patients with familial hypercholesterolemia: Insights from real-world data. American Journal of Preventive Cardiology. 22. doi: 10.1016/j.ajpc.2025.100986. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary heart disease (CHD). While current LDL-C levels usually guides therapy, the cumulative exposure to LDL-C (the LDL-C burden) is suggested to offer a more precise estimate of cardiovascular risk in people with FH. Therefore, using real-world data, this study aimed to estimate the LDL-C burden at different ages in elderly FH patients with and without CHD, and to assess the LDL-C burden at CHD onset. Methods Data was retrospectively collected from the medical records of elderly (>60 years) FH patients at the Lipid Clinic in Oslo. The LDL-C burden (mM-years) was estimated based on repeated LDL-C measurements and information on lipid-lowering medication. Time-weighted average (TWA) LDL-C was calculated as LDL-C burden divided by years. Results We included 112 FH patients, of which 55 (49 %) had experienced at least one CHD-event, and 58 (52 %) were females. Median age at first and last visit were 50 years and 68 years, respectively, with a median of 9 (range; 2–14) available LDL-C measurements. Subjects with CHD had higher LDL-C burden at all ages tested (45, 50 and 60 years) compared with the non-CHD group (p < 0.01, also after adjusting for sex), and had higher TWA LDL-C before treatment at the Lipid Clinic (p = 0.004), but not during follow-up (p = 0.6). There were no sex differences in LDL-C burden at all ages tested, also after adjusting for CHD (p > 0.1). However, women had higher TWA LDL-C during follow-up at the Lipid Clinic (p = 0.01). Median LDL-C burden at CHD onset was 352 mM-years; numerically lower in women than in men (320 vs. 357 mM-years, respectively. p = 0.1). Conclusion Elderly FH patients with CHD had higher estimated LDL-C burden compared with FH patients without CHD, due to higher burden prior to treatment, highlighting the importance of early detection and treatment.

• Narum, Marte; Christensen, Jacob J.; Holven, Kirsten Bjørklund; Berg, Tore Julsrud & Sveen, Kari Anne (2025). Low LDL particle levels associate with coronary arteries free from atherosclerosis in long-term type 1 diabetes: the Dialong study. Cardiovascular Diabetology. 24. doi: 10.1186/s12933-025-02844-z. Fulltekst i vitenarkiv Vis sammendrag

  Background The risk of developing coronary artery disease (CAD) is increased in type 1 diabetes, due to accelerated atherosclerosis. The molecular mechanisms are yet to be unraveled, but potential functional and quantitative abnormalities in lipoproteins are suggested to be involved. Some individuals have coronary arteries free from atherosclerosis even after living with type 1 diabetes for many decades. We therefore aimed to investigate the associations between a set of lipoproteins and metabolites and the presence of coronary arteries free from atherosclerosis in individuals with long-term type 1 diabetes. Methods Cross-sectional, controlled study of 102 participants with type 1 diabetes and 61 control subjects. We used a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform to quantify circulating lipids and metabolites in serum. In participants without previously established coronary heart disease (CHD) we performed computed tomography coronary angiography (CTCA). Results In the diabetes group, mean age was 62 (7) [mean (standard deviation, SD)] year and diabetes duration 50.6 (4.9) years. Lower particle concentration of all LDL subclass particles associated significantly with higher odds of having coronary arteries free from atherosclerosis (p < 0.05). Low particle concentration of all LDL subclasses also associated significantly with normal Coronary Artery Calcium (CAC) score (p < 0.05 for all), after adjustment for age, sex, BMI, eGFR and statin treatment. The whole diabetes group, independent of presence of CAD, had significantly lower particle concentration of IDL and all LDL and VLDL subclass particles compared to the control group (p < 0.05 for all). Conclusions In this cohort of long-term survivors of type 1 diabetes, lower levels of all types of LDL particles associated significantly with higher odds of having coronary arteries free from atherosclerosis, after adjustment for statin treatment. These results emphasize the importance of early treatment start and lipid management in the development of CAD in type 1 diabetes and suggest a subgroup of long-term survivors of type 1 diabetes to may hold environmental or genetic protective beneficial traits, independent of statin use. More research on the role of lipoproteins in the development of atherosclerosis in patients with type 1 diabetes is needed.

• Christensen, Jacob J; Holven, Kirsten Bjørklund; Bogsrud, Martin Prøven; Retterstøl, Kjetil; Lennep, Jeanine E Roeters van & Michelsen, Trond Melbye [Vis alle 8 forfattere av denne artikkelen] (2025). Statin use in pregnancy and risk of congenital malformations: a Norwegian nationwide study. European Heart Journal. ISSN 0195-668X. 47(3), s. 318–327. doi: 10.1093/eurheartj/ehaf592. Fulltekst i vitenarkiv Vis sammendrag

  Background and Aims Statins and other lipid-modifying agents (LMAs) have traditionally been contraindicated during pregnancy due to concerns about harmful fetal effects; however, the risks associated with exposure to statins and other LMAs in human pregnancies remain unclear. Therefore, this study aimed to examine the associations between statin and LMA exposure in pregnancy and congenital malformations in offspring, while updating a 2022 meta-analysis with the results from the present study. Methods National registry data were linked for all pregnant women in Norway in 2005–18. Associations between first-trimester statin prescription fills and congenital malformations were estimated with mixed-effects logistic regression, adjusting for age, parity, pre-pregnancy folate use, smoking in early pregnancy, comorbidity, and co-medication. Meta-analyses were performed with the generic inverse–variance method and random-effects model. Results Congenital malformations occurred among 34 755 out of 803 830 (4.3%) statin non-exposed pregnancies, 74 out of 1255 (5.9%) statin-discontinuer pregnancies, and 19 out of 283 (6.7%) statin-exposed pregnancies. Adjusted odds ratios (ORs) for exposed vs non-exposed pregnancies were 1.30 [95% confidence interval (CI) .81–2.09] for any, 1.15 (.61–2.19) for major, and 1.47 (.75–2.89) for minor malformations. In analyses of exposed vs discontinuer pregnancies, there were no associations between statin exposure and any (adjusted OR 1.01, 95% CI .59–1.72), major (1.08, .52–2.25), or minor malformations (.94, .44–2.00). Results were similar across sensitivity analyses. There was also no association between any LMA exposure and heart malformations (adjusted OR 1.22, 95% CI .50–3.01). The updated meta-analysis suggested no increased risk of major (adjusted OR 1.06, 95% CI .86–1.31) or heart malformations (1.24, 95% CI .94–1.64). Conclusions In this large, nationwide study and updated meta-analysis, no significant association was observed between first-trimester exposure to statins or other LMAs and congenital malformations. Although limited power may have prevented detection of weak but clinically relevant associations, the findings do not support a strong or independent association between statin exposure in pregnancy and congenital malformations.

• Svendsen, Karianne; Christensen, Jacob J.; Igland, Jannicke; Krogh, Henriette Walaas; Mundal, Liv Jorunn & Jacobs, David R. [Vis alle 9 forfattere av denne artikkelen] (2025). Risk of adverse pregnancy outcomes and impact of statin use in pregnant women with familial hypercholesterolemia. Atherosclerosis. ISSN 0021-9150. 408, s. 1–8. doi: 10.1016/j.atherosclerosis.2025.120442. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims Sparse data exist on the risk of adverse pregnancy outcomes in women with familial hypercholesterolemia (FH). We investigated associations between FH and adverse pregnancy outcomes, and between statin exposure in pregnancy and adverse pregnancy outcomes among women with FH. Methods We studied 3869 pregnancies among 1869 women with genetically-proven FH and 68225 pregnancies among 33661 women from the general population. Data on adverse pregnancy outcomes were obtained during 1967–2018 from the Medical Birth Registry of Norway. Data on pharmacy-dispensed statins were obtained from the Norwegian prescription database (2004–2018) in 1051 women with FH. Associations were presented as odds ratio (OR) with 95 % CI from logistic regression adjusted for mother's age, parity, and offspring's birth year. Results Women with FH had a higher risk of preeclampsia (OR 1.21 [1.00–1.46]), but lower risk for gestational diabetes (OR 0.58 [0.36–0.92]) and intrapartum hemorrhage during delivery (OR 0.81 [0.71–0.92]) compared to controls. No excess risk of adverse pregnancy outcomes in offspring was observed for FH. Among women with FH, statin exposure (mainly in the first trimester) may be associated with higher risk of low birth weight in offspring born at term (OR 2.42 [0.51, 11.45]). Conclusions Women with FH had lower risk of gestational diabetes and intrapartum hemorrhage, but a higher risk of preeclampsia compared to controls. No adverse birth outcomes were observed for offspring of mothers with FH, but the association between statin exposure in pregnant women with FH and low birth weight in offspring warrants further study.

• Fossli, Maria; Øhman, Elisabeth Adolfsen; Andal, Malin; Løland, Beate Fossum; Holven, Kirsten Bjørklund & Brekke, Hilde Kristin (2025). Nutrient Intake Among Lactating Women With Overweight and Obesity in Norway: A Comparison With the Nordic Nutrition Recommendations 2023. Journal of human nutrition and dietetics. ISSN 0952-3871. 38(1). doi: 10.1111/jhn.70000. Fulltekst i vitenarkiv Vis sammendrag

  Background During lactation, maternal requirements for many nutrients increase due to the physiological demands of breast milk production, reflected in dietary recommendations. BMI is negatively associated with dietary quality postpartum, and 40% of women in Norway have pre-pregnancy overweight and obesity. Currently, there is limited data on dietary intake among lactating women in Norway and whether they meet nutritional requirements. We aimed to evaluate the nutrient intake in a study sample of lactating women with overweight and obesity, compared with the Nordic Nutrition Recommendations (NNR 2023). Methods In this cross-sectional analysis, we included baseline data from 112 lactating women with a pre-pregnancy BMI of 25–35 kg/m2, participating in a weight loss and breastfeeding promotion intervention trial in Oslo, Norway. Data were collected at 2 weeks postpartum (subject characteristics, anthropometry and dietary supplement use), at 7 weeks postpartum (dietary assessment) and post-weaning (retrospective dietary supplement use). Dietary data were obtained from a 4-day dietary record before randomisation to dietary treatment for weight loss. Nutrient intake was compared to the dietary reference values for lactating women in NNR 2023. Increased risk of inadequate intake of micronutrients was assessed as the proportion of women with intakes below the average requirement (AR), with and without dietary supplements. Results Mean ± SD BMI at 2 weeks postpartum was 30.7 ± 2.5 kg/m2. At 7 weeks postpartum the women reported a mean energy intake of 9.2 ± 2.0 MJ/day, with a higher intake of saturated fat and a lower intake of carbohydrate, dietary fibre and docosahexaenoic acid than recommended. The majority had an increased risk of inadequate intake of vitamin A (92%), folate (92%), vitamin D (84%), selenium (87%) and iodine (71%) from the diet alone. When dietary supplements were taken into account, ≥ 50% of the women still had an increased risk of inadequate intake of vitamin A, folate and selenium. Conclusions The high proportion of lactating women with overweight and obesity failing to meet the newly updated Nordic Nutrition Recommendations highlights the need to raise awareness among new mothers and healthcare professionals about the increased maternal nutritional demands during lactation and hence, the importance of nutrient-dense diets.

• Rundblad, Amanda; Das, Siddhartha; Ginos, Bigina N.R; Matthews, Jason; Holven, Kirsten Bjørklund & Voortman, Trudy [Vis alle 7 forfattere av denne artikkelen] (2025). Exposure to fine particulate matter in adults is associated with immune cell gene expression related to inflammation, the electron transport chain, and cell cycle regulation. Environmental Epigenetics. 11(1). doi: 10.1093/eep/dvaf008. Fulltekst i vitenarkiv Vis sammendrag

  Exposure to air pollution and an unhealthy built environment increase disease risk by impacting metabolic risk factors and inflammation, potentially via epigenetic modifications and effects on gene expression. We aimed to explore associations between fine particulate matter (PM2.5), black carbon, ozone, nitrogen dioxide, distance to nearest water body, normalized difference vegetation index, and impervious surface and gene expression profiles in adults. This study is a part of the LongITools project and includes cross-sectional data from the Rotterdam Study, a population-based cohort study, and NoMa, a randomized controlled trial. Environmental exposures were assigned using land-use regression (LUR) models and satellite data. Gene expression was assessed with whole blood RNA sequencing (Rotterdam Study, n = 758) and microarray analyses in peripheral blood mononuclear cells (NoMa, n = 100). We analysed transcriptomic profiles and enriched pathways associated with each of the environmental exposures. PM2.5 had the strongest gene expression associations, while only a few significant associations were observed for the other environmental exposures. In both populations, exposure to PM2.5 was associated with genes and pathways related to inflammation, oxidative stress, DNA metabolism, cell cycle regulation, histones, electron transport chain, oxidative phosphorylation, and neural signalling. This study is limited by different methods for RNA quantification, a cross-sectional design, and a small sample size. However, in both populations, exposure to PM2.5 resulted in the maximum number of associations with gene expression. In conclusion, PM2.5 is strongly associated with various gene expression profiles, which provide information about the underlying mechanisms of the detrimental health effects of exposure to PM2.5.

• Kristiansen, Anne Lene; Myhre, Jannicke Borch; Øyri, Linn Kristin Lie; Holven, Kirsten Bjørklund & Andersen, Lene Frost (2025). Vitamin D status in Norwegian children and associations between child vitamin D status, dietary factors, and maternal vitamin D status. Food & Nutrition Research (FNR). ISSN 1654-6628. 69. doi: 10.29219/fnr.v69.10727. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims: There is limited data regarding the vitamin D status of infants and young children in Norway. We aimed to assess vitamin D status among Norwegian children at approximately 6 and 12 months of age and explore associations between child vitamin D status, dietary factors, and maternal vitamin D status. Methods: Mothers/parents completed a food frequency questionnaire for their 6/12-month-old child. Dried blood spot samples were collected from the mother and child. Results: The mean serum 25-hydroxyvitamin D (S-25(OH)D) concentration was 81 nmol/L (standard deviation [SD] 22 nmol/L) for 6-month-old children (n = 84) and 72 nmol/L (SD 22 nmol/L) for 12-month-old children (n = 56) (P = 0.03 for difference between age groups). In the younger and older age groups, 94 and 88% of the children, respectively, had a S-25(OH)D concentration ≥ 50 nmol/L. The mean dietary vitamin D intake was 12 μg/day for the 6-month-olds and 14 μg/day for the 12-month-olds. Adjusted linear regression models showed that for every μg/day increase in dietary vitamin D intake, serum 25(OH)D (nmol/L) increased by around one nmol/L for both age groups (P = 0.002 for the younger age group and P = 0.04 for the older age group). Use of vitamin D supplements was associated with higher S-25(OH)D concentrations in both age groups, while a higher S-25(OH)D concentration among formula users was found only in the youngest age group. Breastfeeding was not associated with S-25(OH)D concentration in either age group. Small positive correlations between child and maternal vitamin D status were observed for both the younger (r = 0.22) and the older (r = 0.28) age groups (P = 0.04 for both groups). Conclusion: While there was a wide range in S-25(OH)D concentrations among children, most were within the sufficient range. Adequate vitamin D intake should be encouraged both in the first and second year of life.

• Holven, Kirsten Bjørklund & Sonestedt, Emily (2024). Milk and dairy products - a scoping review for nordic nutrition recommendations 2023. Food & Nutrition Research (FNR). ISSN 1654-6628. 68. doi: 10.29219/fnr.v68.10486. Fulltekst i vitenarkiv Vis sammendrag

  Milk and dairy products are major sources of protein, calcium, and other micronutrients. Milk and dairy products contribute with approximately half of the total intake of saturated fat in the Nordic and Baltic diets. Saturated fat is an important determinant of plasma total and low density lipoprotein (LDL)-cholesterol concentrations, and a causal relationship between high LDL-cholesterol and atherosclerotic cardiovascular disease has consistently been documented. The aim of this scoping review is to describe the evidence for the role of milk and dairy products for health-related outcomes as a basis for setting and updating food-based dietary guidelines. Two qualified systematic reviews were included (World Cancer Research Fund and a systematic review for the US Dietary Guidelines Advisory Committee 2020). In addition, systematic reviews published between January 2011 and January 2022 were considered, screened (555 records) and evaluated (159 records) for this review. The systematic reviews suggest that milk or dairy consumption is not associated with increased risk of cardiovascular disease and dyslipidaemia. Current evidence suggests an inverse association with some cardiometabolic risk factors, such as total and LDL-cholesterol, especially regarding fermented dairy products (i.e. yogurt and cheese). There was evidence of an association between intake of dairy products and reduced risk of colorectal cancer. Some studies reported an inverse association between intake of dairy and type 2 diabetes or markers of impaired glucose homeostasis, especially for low-fat dairy, yoghurt, and cheese. Most studies suggest that intake of milk or dairy is not associated with increased risk of cardiovascular risk and some suggestions of inverse association, especially with low-fat products and fermented dairy products, were found with respect to cardiovascular disease, type 2 diabetes, and colorectal cancer. Milk or dairy products are important dietary sources of calcium and iodine, and are fully compatible with a healthy dietary pattern.

• Jeevanathan, Janeni; Blom, Sigrid Marie; Olsen, Thomas; Holven, Kirsten Bjørklund; Arnesen, Erik Kristoffer & Trydal, Torleif [Vis alle 11 forfattere av denne artikkelen] (2024). Real-world impact of transitioning from one lipoprotein(a) assay to another in a clinical setting. American Journal of Preventive Cardiology. 19. doi: 10.1016/j.ajpc.2024.100726. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims: Different lipoprotein(a) [Lp(a)] assays may affect risk stratification of individuals and thus clinical decision-making. We aimed to investigate how transitioning between Lp(a) assays at a large central laboratory affected the proportion of individuals with Lp(a) result above clinical thresholds. Methods: We studied nationwide clinical laboratory data including 185,493 unique individuals (47.7 % women) aged 18-50 years with 272,463 Lp(a) measurements using Roche (2000-2009) and Siemens Lp(a) assay (2009-2019). Results: While the majority of individuals (66-75 %) had low levels of Lp(a) (<30 mg/dL) independent of the assay used, the Roche assay detected 20 % more individuals with Lp(a) >50 mg/dL, 40 % more individuals with Lp(a) >100 mg/dL and 80 % more individuals with Lp(a) >180 mg/dL than the currently used Siemens assay, likely due to calibration differences. Conclusion: Transitioning from one Lp(a) immunoassay to another had significant impact on Lp(a) results, particularly in individuals approaching clinically relevant Lp(a) thresholds.

• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob Juel; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Vis alle 10 forfattere av denne artikkelen] (2024). Gene expression profiling in elderly patients with familial hypercholesterolemia with and without coronary heart disease. Atherosclerosis. ISSN 0021-9150. 392. doi: 10.1016/j.atherosclerosis.2024.117507. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims Elderly familial hypercholesterolemia (FH) patients are at high risk of coronary heart disease (CHD) due to high cholesterol burden and late onset of effective cholesterol-lowering therapies. A subset of these individuals remains free from any CHD event, indicating the potential presence of protective factors. Identifying possible cardioprotective gene expression profiles could contribute to our understanding of CHD prevention and future preventive treatment. Therefore, this study aimed to investigate gene expression profiles in elderly event-free FH patients. Methods Expression of 773 genes was analysed using the Nanostring Metabolic Pathways Panel, in peripheral blood mononuclear cells (PBMCs) from FH patients ≥65 years without CHD (FH event-free, n = 44) and with CHD (FH CHD, n = 39), and from healthy controls ≥70 years (n = 39). Results None of the genes were differentially expressed between FH patients with and without CHD after adjusting for multiple testing. However, at nominal p < 0.05, we found 36 (5%) differentially expressed genes (DEGs) between the two FH groups, mainly related to lipid metabolism (e.g. higher expression of ABCA1 and ABCG1 in FH event-free) and immune responses (e.g. lower expression of STAT1 and STAT3 in FH event-free). When comparing FH patients to controls, the event-free group had fewer DEGs than the CHD group; 147 (19%) and 219 (28%) DEGs, respectively. Conclusions Elderly event-free FH patients displayed a different PBMC gene expression profile compared to FH patients with CHD. Differences in gene expression compared to healthy controls were more pronounced in the CHD group, indicating a less atherogenic gene expression profile in event-free individuals. Overall, identification of cardioprotective factors could lead to future therapeutic targets.

• Das, Siddhartha; Rundblad, Amanda; Marques, Irene Fontes; Soares, Ana Goncalves; Jaddoe, Vincent W. & Vrijheid, Martine [Vis alle 14 forfattere av denne artikkelen] (2024). Air pollution exposure is associated with gene expression in children. Environmental Epigenetics. 10(1). doi: 10.1093/eep/dvae025. Fulltekst i vitenarkiv Vis sammendrag

  Environmental exposures, including air pollutants and lack of natural spaces, are associated with suboptimal health outcomes in children. We aimed to study the associations between environmental exposures and gene expression in children. Associations of exposure to particulate matter (PM) with diameter <2.5 (PM2.5) and < 10 (PM10) micrometers, nitrogen dioxide, green spaces, and blue space, with whole-blood gene expression were explored in children from the Dutch Generation R Study (n = 172). Analyses were adjusted for age, sex, batch, maternal education, and area socioeconomic status. Follow-up analysis was carried out using lymphoblastoid cell line gene expression in children from the ALSPAC Study (n = 946). Gene set enrichment analysis (GSEA) using hallmark and immune gene sets from the molecular signature database was carried out to identify significantly over-represented gene sets for insights into biological mechanisms Exposure to PM2.5 was associated with expression of 86 genes in discovery analyses in the Generation R Study [false discovery rate (FDR)-adjusted P-value < .25]. Of these, PM2.5 was also associated with GNG11 expression in the same direction in follow-up analysis (FDR-adjusted P-value < .05). The remaining exposures showed much fewer associations in the discovery analyses. GSEA using PM2.5 association results for both cohorts indicated suppression of gene sets related to interferon response and response to bacterial and viral exposure. In conclusion, gene expression analysis performed in two independent cohorts suggests that PM2.5 exposure in children may be involved in interferon and microbial infection responses.

• Bålsrud, Pia; Ulven, Stine Marie; Ottestad, Inger; Retterstøl, Kjetil; Schwab, Ursula & Holven, Kirsten Bjørklund (2024). Association between inflammatory markers, body composition and frailty in home-dwelling elderly: an 8-year follow-up study. GeroScience. ISSN 2509-2715. 46, s. 5629–5641. doi: 10.1007/s11357-024-01279-w. Fulltekst i vitenarkiv Vis sammendrag

  Frailty has been linked to inflammation and changes in body composition, but the findings are inconsistent. To explore this, we used the Frailty Index (FI) definition to (1) investigate the association between levels of inflammatory markers (baseline) and change in FI score after 8 years of follow-up and (2) investigate the longitudinal associations between inflammatory markers, body composition, and frailty. Home-dwelling elderly (≥ 70 years) were invited to participate in the study and re-invited to a follow-up visit 8 years later. This study includes a total of 133 participants. The inflammatory markers included were high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and glycoprotein acetyls (Gp-acetyls). We used the body composition markers fat mass, fat-free mass, and waist circumference. The FI score consisted of 38 variables. Additional clinical assessments such as blood pressure and body mass index (BMI), as well as information about daily medications, were collected at both visits. Linear regression model and Spearman’s rank correlation were used to investigate associations. We showed that the FI score increased after 8 years, and participants with higher hs-CRP levels at baseline had the largest change in the FI score. Changes in fat mass were significantly correlated with changes in hs-CRP and IL-6, and changes in waist circumference were significantly correlated with changes in TNF-α. The use of drugs increased during the 8 years of follow-up, which may have attenuated the associations between inflammation and frailty. However, elevated concentrations of hs-CRP in the elderly may be associated with an increased risk of frailty in subsequent years.

• Rønning, Sissel Beate; Carlsen, Harald; Rocha, Sergio Domingos Cardoso; Rud, Ida; Solberg, Nina & Høst, Vibeke [Vis alle 18 forfattere av denne artikkelen] (2024). Dietary intake of micronized avian eggshell membrane in aged mice reduces circulating inflammatory markers, increases microbiota diversity, and attenuates skeletal muscle aging. Frontiers in Nutrition. 10, s. 1–19. doi: 10.3389/fnut.2023.1336477. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Avian eggshell membrane (ESM) is a complex extracellular matrix comprising collagens, glycoproteins, proteoglycans, and hyaluronic acid. We have previously demonstrated that ESM possesses anti-inflammatory properties in vitro and regulates wound healing processes in vivo. The present study aimed to investigate if oral intake of micronized ESM could attenuate skeletal muscle aging associated with beneficial alterations in gut microbiota profile and reduced inflammation. Methods: Elderly male C57BL/6 mice were fed an AIN93G diet supplemented with 0, 0.1, 1, or 8% ESM. Young mice were used as reference. The digestibility of ESM was investigated using the static in vitro digestion model INFOGEST for older people and adults, and the gut microbiota profile was analyzed in mice. In addition, we performed a small-scale pre-clinical human study with healthy home-dwelling elderly (>70 years) who received capsules with a placebo or 500 mg ESM every day for 4 weeks and studied the effect on circulating inflammatory markers. Results and discussion: Intake of ESM in elderly mice impacted and attenuated several well-known hallmarks of aging, such as a reduction in the number of skeletal muscle fibers, the appearance of centronucleated fibers, a decrease in type IIa/IIx fiber type proportion, reduced gene expression of satellite cell markers Sdc3 and Pax7 and increased gene expression of the muscle atrophy marker Fbxo32. Similarly, a transition toward the phenotypic characteristics of young mice was observed for several proteins involved in cellular processes and metabolism. The digestibility of ESM was poor, especially for the elderly condition. Furthermore, our experiments showed that mice fed with 8% ESM had increased gut microbiota diversity and altered microbiota composition compared with the other groups. ESM in the diet also lowered the expression of the inflammation marker TNFA in mice and in vitro in THP-1 macrophages. In the human study, intake of ESM capsules significantly reduced the inflammatory marker CRP. Altogether, our results suggest that ESM, a natural extracellular biomaterial, may be attractive as a nutraceutical candidate with a possible effect on skeletal muscle aging possibly through its immunomodulating effect or gut microbiota.

• Johansen, Anja Katrin; Bogsrud, Martin Prøven; Thoresen, Magne; Christensen, Jacob J.; Narverud, Ingunn & Langslet, Gisle [Vis alle 9 forfattere av denne artikkelen] (2024). Lipoprotein(a) in children and adolescents with genetically confirmed familial hypercholesterolemia followed up at a specialized lipid clinic. Atherosclerosis Plus. ISSN 2667-0909. 57, s. 13–18. doi: 10.1016/j.athplu.2024.06.002. Fulltekst i vitenarkiv Vis sammendrag

  Background and aim Many children with an FH mutation also exhibit elevated lipoprotein(a) levels, which is an independent risk factor for atherosclerotic cardiovascular disease. Studies have reported higher levels of lipoprotein(a) in adult and middle-aged women than men. There is limited knowledge on the concentration and change of lipoprotein(a) levels in children with genetic FH, and therefore we investigated sex-differences in lipoprotein(a) level and change in lipoprotein(a) in girls and boys with genetically confirmed FH. Methods Medical records were reviewed retrospectively in 438 subjects with heterozygous FH that started follow-up below the age of 19 years at the Lipid Clinic, Oslo University Hospital in Norway, and of these we included 386 subjects with at least one Lp(a) measurement. Results Mean (SD) age at baseline was 13.8 (7.3) years and the age was similar between sexes. Girls had a higher lipoprotein(a) level than boys at baseline: median (25–75 percentile) 223 (108–487) vs. 154 (78–360) mg/L, respectively (p < 0.01). From baseline to follow-up measurement (mean [SD] 8.9 [6.1] years apart), the mean (95 % CI) absolute and percentage change in Lp(a) level in girls was 151.4 (54.9–247.8) mg/L and 44.8 (16.4–73.1) %, respectively, and in boys it was 66.8 (22.9–110.8) mg/L and 50.5 (8.8–92.3) %, respectively (both p > 0.05). Conclusions We found an increase in Lp(a) levels in children with genetic FH with age, and higher levels in girls than boys, which could impact risk assessment and future ASCVD. Further research is needed to elucidate whether subjects with FH could benefit from lipoprotein(a)-lowering therapies that are under current investigations.

• Løvheim, Eirin Brenna; Retterstøl, Kjetil; Narverud, Ingunn; Bogsrud, Martin Prøven; Halvorsen, Bente & Ueland, Thor [Vis alle 8 forfattere av denne artikkelen] (2024). Adherence to the Healthy Nordic Food Index is associated with reduced plasma levels of inflammatory markers in patients with heterozygous familial hypercholesterolemia. Atherosclerosis Plus. ISSN 2667-0909. 58, s. 38–45. doi: 10.1016/j.athplu.2024.10.003. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims Familial hypercholesterolemia (FH) is an inherited disease associated with hypercholesterolemia, and dietary treatment is part of the treatment. We aimed to assess the dietary pattern in relation to the Healthy Nordic Food Index (HNFI) in adults with and without heterozygous FH (HeFH), and to examine the associations between dietary quality and biomarkers related to cardiovascular disease in adults with HeFH. Methods We included 205 adults (≥18 years) with HeFH who received follow-up at the Lipid Clinic in Oslo and compared them to controls (n = 228). Dietary intake was assessed using a food frequency questionnaire and dietary quality was assessed using the HNFI. Blood samples were analysed for levels of blood lipids, plasma fatty acids (FAs), and markers of inflammation and platelet activation. Results The HeFH patients (median 60 years; 50.2 % female; 25.9 % in secondary prevention) had lower intake of total and saturated fat compared to controls (32.6 energy percent (E%) vs. 34.9 E%, and 9.6 E% vs 12.0 E%, respectively; p < 0.001 for both). In the HeFH patients, increasing dietary quality was associated with increased plasma levels of the n-3 polyunsaturated FAs (PUFAs) eicosapentaenoic acid and docosahexaenoic acid, and the n-6 PUFA linoleic acid, and lower plasma levels of the inflammatory cytokines Tumor Necrosis Factor and interleukin-6, and of the platelet-derived inflammatory cytokines Platelet Factor 4 and Neutrophil-Activating Peptide-2. Conclusion Norwegian patients with HeFH followed up at a Lipid Clinic eat healthier than controls. Adherence to a healthy dietary pattern is associated with higher plasma levels of n-3 and n-6 PUFA, and lower levels of inflammatory markers, including platelet markers. This may suggest that adherence to an overall healthy dietary pattern might be beneficial for HeFH patients independent of the cholesterol-lowering effect of the diet.

• Michelsen, Trond Melbye; Skytte, Hege Nyhus; Gunnes, Nina; Holven, Kirsten Bjørklund; Christensen, Jacob J. & Roland, Marie Cecilie (2024). Metabolic profiles in early pregnancy associated with metabolic pregnancy complications in women with obesity. Journal of Reproductive Immunology. ISSN 0165-0378. 166. doi: 10.1016/j.jri.2024.104397. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Higher maternal body mass index (BMI) is associated with metabolic disturbances and pregnancy complications. We aimed to examine whether metabolic profiles in early pregnancy were associated with metabolic pregnancy complications in women with obesity (BMI ≥ 30 kg/m2). Material and methods Nested cohort study from a prospective longitudinal cohort (n = 1031) of women who were healthy prior to pregnancy and gave birth at Oslo University Hospital from 2002–2008. The sample comprised 81 women with obesity. Metabolic pregnancy complications included gestational diabetes mellitus, gestational hypertension and preeclampsia. In plasma samples from gestational weeks 14–16, 91 metabolites were analyzed by nuclear magnetic resonance spectroscopy. We performed a principal component analysis to reduce the metabolic dimensions. Logistic regression models were fitted to estimate crude and adjusted odds ratios (ORs) of metabolic pregnancy complications. Results Twenty-four out of 81 women developed metabolic pregnancy complications (gestational hypertension, preeclampsia, and/or gestational diabetes). Two of five principal components (80 % explained variance) were significantly associated with metabolic pregnancy complications. The ratio of monounsaturated to total fatty acids increased the risk of metabolic pregnancy complications (OR 2.09, 95 % confidence interval [CI] 1.25–3.75), while the ratio of polyunsaturated to monounsaturated fatty acids decreased the risk (OR 0.54, 95 % CI 0.30–0.89). The ratio of omega-3 to total fatty acids (OR 0.59, 95 % CI 0.34–0.98) and the ratio of docosahexaenoic acid to total fatty acids (OR 0.57, 95 % CI 0.31–0.97) also decreased the risk of metabolic pregnancy complications. Conclusion Metabolic profile in early pregnancy was associated with risk of metabolic pregnancy complications in women with obesity. We observed the strongest associations between fatty acid composition and metabolic pregnancy complications.

• Øhman, Elisabeth Adolfsen; Fossli, Maria; Rasmussen, Kathleen M.; Winkvist, Anna; Løland, Beate Fossum & Holven, Kirsten Bjørklund [Vis alle 7 forfattere av denne artikkelen] (2024). Effects of Breastfeeding Promotion Intervention and Dietary Treatment in Postpartum Women with Overweight and Obesity: Results from a Randomized Controlled Trial on Weight and Cardiometabolic Risk Factors. Journal of Nutrition. ISSN 0022-3166. 154(8), s. 2448–2458. doi: 10.1016/j.tjnut.2024.06.006. Fulltekst i vitenarkiv Vis sammendrag

  Background Childbearing increases the risk of weight gain and cardiometabolic disease. The reset hypothesis suggests that lactation has protective cardiometabolic effects on the mother. The hypothesis is based on observational studies, and the possible interacting role of weight loss needs to be elucidated. Objectives This study aimed to examine the individual and interaction effects of a breastfeeding promotion intervention (BPI) and dietary intervention for weight loss postpartum (Diet) on body weight and cardiometabolic risk factors at 6 mo postpartum. Methods Pregnant women (n = 156) with a prepregnancy BMI of 25 to 35 kg/m2 were randomized to 4 groups in a 2 × 2 factorial design: BPI, Diet, both treatments, or no treatment. BPI consisted of individual counseling by a lactation consultant during pregnancy, at childbirth, and monthly thereafter or more frequently based on individual needs. Diet was initiated at 11 wk postpartum. Body weight, body composition, waist and hip circumferences, markers of lipid and glucose metabolism, and blood pressure were measured at 2 wk and 6 mo postpartum. We analyzed main and interaction effects using 2-way analysis of covariance adjusted for baseline values. Results Among the participants attending both visits (n = 108), 99% practiced any breastfeeding at baseline and 97% at follow-up. The BPI did not affect rates of exclusive or partial breastfeeding, age at introduction of complementary foods, or have main effects on body weight or cardiometabolic risk factors. There was a main effect of Diet reducing body weight, fat mass, fat-free mass, percentage fat mass, waist and hip circumferences, fasting glucose, and insulin (all P ≤ 0.03), with no interactions between the treatments. Conclusions There were no effects of BPI on body weight or cardiometabolic risk factors at 6 mo postpartum. Diet caused weight loss and had favorable effects on risk factors for cardiovascular disease and type 2 diabetes.

• Bålsrud, Pia; Ulven, Stine Marie; Christensen, Jacob J.; Ottestad, Inger & Holven, Kirsten Bjørklund (2024). Inflammatory markers and frailty in home-dwelling elderly, a cross-sectional study. BMC Geriatrics. 24(1), s. 1–11. doi: 10.1186/s12877-024-04690-2. Fulltekst i vitenarkiv Vis sammendrag

  Background Low-grade, chronic inflammation during ageing, (“inflammageing”), is suggested to be involved in the development of frailty in older age. However, studies on the association between frailty, using the frailty index definition, and inflammatory markers are limited. The aim of this study was to investigate the relationship between inflammatory markers and frailty index (FI) in older, home-dwelling adults. Method Home-dwelling men and women aged ≥ 70 years old, living in South-East Norway were recruited and included in a cross-sectional study. The FI used in the current study was developed according to Rockwood’s frailty index and included 38 variables, resulting in an FI score between 0 and 1 for each participant. Circulating inflammatory markers (IL-6, CRP, IGF-1, cystatin C, cathepsin S, and glycoprotein Acetyls) were analyzed from non-fasting blood samples using ELISA. Whole-genome PBMC transcriptomics was used to study the association between FI score and inflammation. Results The study population comprised 403 elderly (52% women), with a median age of 74 years and a mean BMI of 26.2 kg/m2. The mean FI score for the total group was 0.15 (range 0.005–0.56). The group was divided into a frail group (FI score ≥ 0.25) and non-frail group. After adjusting for BMI, age, sex, and smoking in the whole group, IL-6, cathepsin S, cystatin C, and Gp-acetyls remained significant associated to FI score (IL-6: 0.002, 95% CI: 0.001, 0.002, cathepsin S: 6.7e-06, 95% CI 2.44e-06, 0.00001, cystatin C: 0.004, 95% CI: 0.002, 0.006, Gp- Acetyls: 0.09, 95% CI: 0.05, 0.13, p < 0.01 for all), while CRP and IGF-1 were not (0.0003, 95% CI: -00001, 0.0007, p = 0.13, (-1.27e-06), 95% CI: (-0.0003), 0.0003, p = 0.99). There was a significant association between FI score and inflammatory markers, and FI score and monocyte-specific gene expression. Conclusions We found an association between FI score and inflammatory markers, and between FI score and monocyte-specific gene expression among elderly subjects above 70 years of age. Whether inflammation is a cause or consequence of frailty and whether the progression of frailty can be attenuated by reducing inflammation remains to be clarified.

• Gregersen, Ida; Kong, Xiang Yi; Kooijman, Sander; Foyn, Håvard; Grannes, Helene & Olsen, Maria Belland [Vis alle 25 forfattere av denne artikkelen] (2024). T cells with increased responsiveness cause obesity in mice without diet intervention. iScience. 27(4). doi: 10.1016/j.isci.2024.109471. Fulltekst i vitenarkiv Vis sammendrag

  Obesity is a complex multicausal disease that can cause morbidity and mortality, and there is need for improved knowledge on the underlying mechanisms. Using a mouse model of increased T cell responsiveness, we show that development of obesity can be driven by immune cells. This was confirmed with bone marrow transplantation and adoptive T cell transfer to several recipient mouse models. Single-cell RNA sequencing and CyTOF analysis showed that the mice display altered composition of circulating T cells and increased T cell activation in visceral adipose tissue, suggesting activated T cells as critical players in the increased fat mass. In this study, we provide evidence that obesity can be driven by immune cell activity and in particular by T cells, which could have broad implications for prevention and treatment of this condition.

• Olsen, Maria Belland; Louwe, Maria; Yang, Kuan; Øgaard, Jonas Daniel Sjøberg; Dahl, Tuva Børresdatter & Gregersen, Ida [Vis alle 16 forfattere av denne artikkelen] (2024). Continuous infusion of resolvin D2 in combination with Angiotensin-II show contrary effects on blood pressure and intracardiac artery remodeling. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 733. doi: 10.1016/j.bbrc.2024.150706. Fulltekst i vitenarkiv Vis sammendrag

  Specialized pro-resolving mediators (SPMs) are key effectors of resolution of inflammation. This is highly relevant for cardiac and vessel remodeling, where the net inflammatory response contributes to determine disease outcome. Herein, we used a mice model of angiotensin (Ang)–II–induced hypertension to study the effect of the SPM Resolvin D2 (RvD2), on hypertension and cardiac remodeling. By using subcutaneous osmotic minipumps, mice were treated with PBS or Ang-II in combination with or without RvD2 for two weeks. Mice receiving RvD2 gained less blood pressure increase compared to Ang-II alone. Surprisingly, however, examination of intracardiac arteries revealed that RvD2 treatment in combination with Ang-II exacerbated Ang–II–induced fibrosis. Measures of vascular smooth muscle cell dedifferentiation correlated with the level of vascular remodeling, indicating that this dedifferentiation, including increased proliferation and migration, is a contributing factor. RNA sequencing of left ventricle cardiac tissue supported these findings as pathways related to cell proliferation and cell differentiation were upregulated in mice treated with Ang-II in combination with RvD2. Additionally, the RNA sequencing also showed upregulation of pathways related to SPM metabolism. In line with this, Mass spectrometry analysis of lipid mediators showed reduced cardiac levels of the arachidonic acid derived metabolite leukotriene E4 in RvD2 treated mice. Our study suggests that continuous infusion through osmotic minipumps should not be the recommended route of RvD2 administration in future studies.

• Gregersen, Ida; Narverud, Ingunn; Christensen, Jacob J.; Hovland, Anders Wilhelm; Øyri, Linn Kristin Lie & Ueland, Thor [Vis alle 11 forfattere av denne artikkelen] (2024). Plasma legumain in familial hypercholesterolemia: associations with statin use and cardiovascular risk markers. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 84(1), s. 24–29. doi: 10.1080/00365513.2024.2309617. Fulltekst i vitenarkiv Vis sammendrag

  Legumain is known to be regulated in atherosclerotic disease and may have both pro- and anti-atherogenic properties. The study aimed to explore legumain in individuals with familial hypercholesterolemia (FH), a population with increased cardiovascular risk. Plasma legumain was measured in 251 subjects with mostly genetically verified FH, of which 166 were adults (≥18 years) and 85 were children and young adults (<18 years) and compared to 96 normolipidemic healthy controls. Plasma legumain was significantly increased in the total FH population compared to controls (median 4.9 versus 3.3 pg/mL, respectively, p < 0.001), whereof adult subjects with FH using statins had higher levels compared to non-statin users (5.7 versus 3.9 pg/mL, respectively, p < 0.001). Children and young adults with FH (p = 0.67) did not have plasma legumain different from controls at the same age. Further, in FH subjects, legumain showed a positive association with apoB, and markers of inflammation and platelet activation (i.e. fibrinogen, NAP2 and RANTES). In the current study, we show that legumain is increased in adult subjects with FH using statins, whereas there was no difference in legumain among children and young adults with FH compared to controls. Legumain was further associated with cardiovascular risk markers in the FH population. However the role of legumain in regulation of cardiovascular risk in these individuals is still to be determined.

• Myhrstad, Mari Charlotte Wik; Ruud, Emilia; Gaundal, Line; Gjøvaag, Terje; Rud, Ida & Retterstøl, Kjetil [Vis alle 10 forfattere av denne artikkelen] (2024). Gut microbiota, physical activity and/or metabolic markers in healthy individuals - towards new biomarkers of health. Frontiers in Nutrition. 11, s. 1–8. doi: 10.3389/fnut.2024.1438876. Fulltekst i vitenarkiv Vis sammendrag

  Background: The global prevalence of the metabolic disease Type 2 Diabetes (T2D) is increasing. Risk factors contributing to the development of T2D include overweight and obesity, lack of physical activity (PA), and an unhealthy diet. In addition, the gut microbiota has been shown to affect metabolic regulation. Since T2D is preventable, efforts should be put into the discovery of new biomarkers for early detection of individuals at risk of developing the disease. Objective: The objective of the cross-sectional study was to explore the relationship between gut microbiota and physical activity (PA) and/or metabolic markers such as selected amino acids (AA), markers of glycaemic regulation and lipid metabolism and anthropometric measures. Design: Healthy adults (18 and 65 years) with BMI between 18.5 and 27.5 kg/m2 originally recruited to a randomised controlled trial (RCT) (n = 17: six males, eleven females), were included in this exploratory cross-sectional study. Physical activity data was calculated based on a 3-days registration, and blood metabolome, gut microbiota analyses and anthropometric measures from one visit of the intervention were used in this cross-sectional study. Results: Of the 47 gut bacteria analysed, there were a total of 87 significant correlations with AA, PA, body composition and/or metabolic markers. Several of the gut bacteria correlated with both PA, metabolic or anthropometric markers. Conclusion: In this study, we demonstrate associations between gut bacteria and PA and/or metabolic markers including AA in healthy individuals. The results may guide future studies aiming at identifying new and early biomarkers of metabolic health and diseases.

• Sousa, Ana Rita Sequeira de; Ottestad, Inger; Gjevestad, Gyrd Omholt; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Christensen, Jacob J. (2023). Associations between PBMC whole genome transcriptome, muscle strength, muscle mass, and physical performance in healthy home-dwelling older women. GeroScience. ISSN 2509-2715. 45, s. 3175–3186. doi: 10.1007/s11357-023-00819-0. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Increasing age is accompanied by many changes, including declining functional skeletal muscle health and immune dysfunction. Peripheral blood mononuclear cells (PBMCs) are circulating cells that assemble an immune response, but their whole genome transcriptome has not been studied in the context of age-related muscle health. Consequently, this article explored associations between three muscle variables indicative of functional muscle health — maximum handgrip strength (muscle strength), appendicular skeletal muscle mass index (ASMI, muscle mass), and gait speed (physical performance) — and two groups of bioinformatics-generated PBMC gene expression features (gene expression–estimated leukocyte subset proportions and gene clusters). We analyzed cross-sectional data from 95 home-dwelling healthy women ≥ 70 years, using “cell-type identification by estimating relative subsets of RNA transcripts” (CIBERSORT) to estimate leukocyte subset proportions and “weighted correlation network analysis” (WGCNA) to generate gene clusters. Associations were studied using linear regression models and relevant gene clusters were subjected to gene set enrichment analysis using gene ontology. Gait speed and ASMI associated with CIBERSORT-estimated monocyte proportions ( β  =  − 0.090, 95% CI = (− 0.146, − 0.034), p -value = 0.002 for gait speed, and β  =  − 0.206, 95% CI = (− 0.385, − 0.028), p -value = 0.024 for ASMI), and gait speed associated with CIBERSORT-estimated M2 macrophage proportions ( β  =  − 0.026, 95% CI = (− 0.043, − 0.008), p -value = 0.004). Furthermore, maximum handgrip strength associated with nine WGCNA gene clusters, enriched in processes related to immune function and skeletal muscle cells ( β in the range − 0.007 to 0.008, p -values &lt; 0.05). These results illustrate interactions between skeletal muscle and the immune system, supporting the notion that age-related functional muscle health and the immune system are closely linked.

• Johansen, Anja Katrin; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Ulven, Stine Marie [Vis alle 9 forfattere av denne artikkelen] (2023). Young women with familial hypercholesterolemia have higher LDL-cholesterol burden than men: Novel data using repeated measurements during 12-years follow-up. Atherosclerosis Plus. ISSN 2667-0909. 51, s. 28–34. doi: 10.1016/j.athplu.2023.01.001. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims The concentration and the duration of exposure to low-density lipoprotein cholesterol (LDL-C) (LDL-C burden) is an important determinant of risk for cardiovascular disease and thresholds has recently been estimated. Individuals with familial hypercholesterolemia (FH) have increased risk of premature cardiovascular disease. The overall aim of the present study was to describe differences in LDL-C level and LDL-C burden in females and males with FH visiting an outpatient lipid clinic from a young age, using multiple LDL-C measurements during a follow-up time of 12 years. First, we aimed to study if the LDL-C concentration and the LDL-C burden is different between females and males at ages 0–10, 10–20, 20–30 and >30 years. Second, we aimed to estimate the subject-specific LDL-C burden at age 19 and 30 years, and the proportion of female and male patients that reach suggested LDL-C thresholds indicating high risk of ASCVD. Methods Data was retrospectively collected from medical records of 438 subjects (207 girls and 231 boys) with FH, referred to the Lipid Clinic, Oslo University Hospital below the age of 19 years. The LDL-C burden was estimated based on repeated LDL-C measurements over time. Results Subjects were followed over a period of mean 12.0 (SD 7.0) years, with median 10 years (7–17; 25–75 percentiles, minimum 2), with median 6 (4–9; 25–75 percentiles, minimum 2) available LDL-C measurements, starting at mean age 11 (SD 3.9) years. There was a difference in both LDL-C and LDL-C burden between sexes at different ages. On average, males had lower LDL-C over time, although this difference was less pronounced with age and males also had lower estimated LDL-C burden over time, and this difference was further exacerbated with age. Conclusion Our study shows that young women with FH have a higher LDL-C burden than their male counterparts, potentially explaining the increased excess CVD risk seen among these. It underscores the importance of careful-follow up and early treatment initiation both prior to and after pregnancies in order to limit statin-free periods.

• Rundblad, Amanda; Sandoval, Viviana Paz Sandoval; Holven, Kirsten Bjørklund; Ordovás, José M. & Ulven, Stine Marie (2023). Omega-3 fatty acids and individual variability in plasma triglyceride response: A mini-review. Redox Biology. 63, s. 1–9. doi: 10.1016/j.redox.2023.102730. Fulltekst i vitenarkiv Vis sammendrag

  Cardiovascular disease (CVD) is a leading cause of death worldwide. Supplementation with the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with lower CVD risk. However, results from randomized controlled trials that examine the effect of omega-3 supplementation on CVD risk are inconsistent. This risk-reducing effect may be mediated by reducing inflammation, oxidative stress and serum triglyceride (TG) levels. However, not all individuals respond by reducing TG levels after omega-3 supplementation. This inter-individual variability in TG response to omega-3 supplementation is not fully understood. Hence, we aim to review the evidence for how interactions between omega-3 fatty acid supplementation and genetic variants, epigenetic and gene expression profiling, gut microbiota and habitual intake of omega-3 fatty acids can explain why the TG response differs between individuals. This may contribute to understanding the current controversies and play a role in defining future personalized guidelines to prevent CVD.

• Øyri, Linn K. L.; Christensen, Jacob J.; Sebert, Sylvain; Thoresen, Magne; Michelsen, Trond M. & Ulven, Stine M. [Vis alle 12 forfattere av denne artikkelen] (2023). Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study. BMC Medicine. 21. doi: 10.1186/s12916-023-02742-9. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Vis alle 7 forfattere av denne artikkelen] (2023). Dietary treatment postpartum in women with obesity reduces weight and prevents weight gain: a randomised controlled trial. BMC Pregnancy and Childbirth. 23. doi: 10.1186/s12884-023-05976-w. Fulltekst i vitenarkiv Vis sammendrag

  Background Women with pre-pregnancy obesity have an increased risk of retaining or gaining weight postpartum and may benefit from weight loss treatment. However, evidence is lacking for weight loss strategies in women with BMIs in the higher obesity classes. A dietary treatment for postpartum weight loss resulted in a 10% weight reduction in lactating women with a mean BMI of 30 kg/m2. We aimed to examine the effects of this dietary treatment on changes in weight, markers of lipid and glucose metabolism, waist and hip circumference and postpartum weight retention (PPWR) in postpartum women with higher BMIs than tested previously. Methods At baseline, approximately 8 weeks postpartum, 29 women with a mean (SD) BMI = 40.0 (5.2) kg/m2 were randomised to a 12-week dietary treatment (n 14) or to a control treatment (n 15). Measurements were made at baseline and after 3 and 12 months. Data was analysed using mixed model. Results The mean weight change in the diet group was -2.3 (3.1) kg compared to 1.7 (3.1) kg in the control group after 3 months (P = 0.003) and -4.2 (5.6) kg compared to 4.8 (11.8) kg in the control group after 12 months (P = 0.02). The dietary treatment led to reduced waist circumference (P < 0.04) and PPWR (P < 0.01) compared to the control treatment at both time points. The treatment lowered fasting blood glucose at 12 months (P = 0.007) as the only effect on markers of lipid and glucose metabolism. Conclusion The dietary treatment postpartum reduced weight and prevented weight retention or weight gain in women with obesity. Trial registration The trial was retrospectively registered at ClinicalTrials.gov (NCT03579667) 06/07/2018. Graphical Abstract In a randomised, controlled trial, 29 postpartum women with obesity were allocated to a dietary treatment or a control treatment. The dietary treatment reduced weight and prevented postpartum weight retention or weight gain after 12 months. Reference: Adapted from “Randomized, Placebo-Controlled, Parallel Study Design (2 Arms, Graphical)”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates .

• Skytte, Hege; Roland, Marie Cecilie; Christensen, Jacob J.; Holven, Kirsten Bjørklund; Lekva, Tove & Gunnes, Nina [Vis alle 7 forfattere av denne artikkelen] (2023). Maternal metabolic profiling across body mass index groups: An exploratory longitudinal study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 103(3), s. 540–550. doi: 10.1111/aogs.14750. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Introduction Increased BMI has been identified as a risk factor for most pregnancy complications, but the underlying metabolic factors mediating the detrimental effects of BMI are largely unknown. We aimed to compare metabolic profiles in overweight/obese women (body mass index [BMI] ≥ 25 kg/m 2 ) and normal weight/underweight women (BMI &lt; 25 kg/m 2 ) across gestation. We also explored how gestational weight gain (GWG) affected maternal metabolic profiles. Material and methods Exploratory nested case–control study based on a prospective longitudinal cohort of women who were healthy prior to pregnancy and gave birth at Oslo University Hospital from 2002 to 2008. The sample consisted of 48 women who were overweight/obese and 59 normal‐weight/underweight women. Plasma samples from four time points in pregnancy (weeks 14–16, 22–24, 30–32 and 36–38) were analyzed by nuclear magnetic resonance spectroscopy and 91 metabolites were measured. Linear regression models were fitted for each of the metabolites at each time point. Results Overweight or obese women had higher levels of lipids in very‐low‐density lipoprotein (VLDL), total triglycerides, triglycerides in VLDL, total fatty acids, monounsaturated fatty acids, saturated fatty acids, leucine, valine, and total branched‐chain amino acids in pregnancy weeks 14–16 compared to underweight and normal‐weight women. Docosahexaenoic acid and degree of unsaturation were significantly lower in overweight/obese women in pregnancy weeks 36–38. In addition, overweight or obese women had higher particle concentration of XXL‐VLDL and glycoprotein acetyls (GlycA) at weeks 14–16 and 30–32. GWG did not seem to affect the metabolic profile, regardless of BMI group when BMI was treated as a dichotomous variable, ≥25 kg/m 2 (yes/no). Conclusions Overweight or obese women had smaller pregnancy‐related metabolic alterations than normal‐weight/underweight women. There was a trend toward higher triglyceride and VLDL particle concentration in overweight/obese women. As this was a hypothesis‐generating study, the similarities with late‐onset pre‐eclampsia warrant further investigation. The unfavorable development of fatty acid composition in overweight/obese women, with possible implication for the offspring, should also be studied further in the future.

• Holven, Kirsten Bjørklund & Lennep, Jeanine Roeters van (2023). Sex differences in lipids: A life course approach. Atherosclerosis. ISSN 0021-9150. 384. doi: 10.1016/j.atherosclerosis.2023.117270. Fulltekst i vitenarkiv
• Macpherson, Magnhild Eide; Skarpengland, Tonje; Hov, Johannes Espolin Roksund; Ranheim, Trine; Vestad, Beate & Dahl, Tuva Børresdatter [Vis alle 14 forfattere av denne artikkelen] (2023). Increased Plasma Levels of Triglyceride-Enriched Lipoproteins Associate with Systemic Inflammation, Lipopolysaccharides, and Gut Dysbiosis in Common Variable Immunodeficiency. Journal of Clinical Immunology. ISSN 0271-9142. 43, s. 1229–1240. doi: 10.1007/s10875-023-01475-x. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: Triglycerides (TG) and their major transport lipoprotein in the circulation (VLDL) appear to be related to inflammation. Patients with common variable immunodeficiency (CVID) have inflammatory complications associated with gut microbial dysbiosis. We hypothesized that CVID patients have disturbed TG/VLDL profiles associated with these clinical characteristics. Methods: We measured plasma concentrations of TGs, inflammatory markers, and lipopolysaccharide (LPS) in 95 CVID patients and 28 healthy controls. Additionally, in 40 CVID patients, we explored plasma lipoprotein profiling, fatty acid, gut microbial dysbiosis, and diet. Results: TG levels were increased in CVID patients as compared to healthy controls (1.36 ± 0.53 mmol/l versus 1.08 ± 0.56 [mean, SD], respectively, P = 0.008), particularly in the clinical subgroup “Complications,” characterized by autoimmunity and organ-specific inflammation, compared to “Infection only” (1.41 mmol/l, 0.71[median, IQR] versus [1.02 mmol/l, 0.50], P = 0.021). Lipoprotein profile analyses showed increased levels of all sizes of VLDL particles in CVID patients compared to controls. TG levels correlated positively with CRP (rho = 0.256, P = 0.015), IL-6 (rho = 0.237, P = 0.021), IL-12 (rho = 0.265, P = 0.009), LPS (r = 0.654, P = 6.59 × 10−13), CVID-specific gut dysbiosis index (r = 0.315, P = 0.048), and inversely with a favorable fatty acid profile (docosahexaenoic acid [rho =  − 0.369, P = 0.021] and linoleic acid [rho =  − 0.375, P = 0.019]). TGs and VLDL lipids did not appear to be associated with diet and there were no differences in body mass index (BMI) between CVID patients and controls. Conclusion: We found increased plasma levels of TGs and all sizes of VLDL particles, which were associated with systemic inflammation, LPS, and gut dysbiosis in CVID, but not diet or BMI.

• Lennep, Jeanine E. Roeters Van; Tokgözoǧlu, Lale S.; Badimon, Lina; Dumanski, Sandra M.; Gulati, Martha & Hess, Connie N. [Vis alle 16 forfattere av denne artikkelen] (2023). Women, lipids, and atherosclerotic cardiovascular disease: a call to action from the European Atherosclerosis Society. European Heart Journal. ISSN 0195-668X. 44(39), s. 4157–4173. doi: 10.1093/eurheartj/ehad472. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Cardiovascular disease is the leading cause of death in women and men globally, with most due to atherosclerotic cardiovascular disease (ASCVD). Despite progress during the last 30 years, ASCVD mortality is now increasing, with the fastest relative increase in middle-aged women. Missed or delayed diagnosis and undertreatment do not fully explain this burden of disease. Sex-specific factors, such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency), and polycystic ovary syndrome are also relevant, with good evidence that these are associated with greater cardiovascular risk. This position statement from the European Atherosclerosis Society focuses on these factors, as well as sex-specific effects on lipids, including lipoprotein(a), over the life course in women which impact ASCVD risk. Women are also disproportionately impacted (in relative terms) by diabetes, chronic kidney disease, and auto-immune inflammatory disease. All these effects are compounded by sociocultural components related to gender. This panel stresses the need to identify and treat modifiable cardiovascular risk factors earlier in women, especially for those at risk due to sex-specific conditions, to reduce the unacceptably high burden of ASCVD in women.

• Schreuder, M.M.; Hamkour, S.; Siegers, K.E.; Holven, Kirsten Bjørklund; Johansen, Anja Katrin & Ree, de van de [Vis alle 14 forfattere av denne artikkelen] (2023). LDL cholesterol targets rarely achieved in familial hypercholesterolemia patients: A sex and gender-specific analysis. Atherosclerosis. ISSN 0021-9150. 384. doi: 10.1016/j.atherosclerosis.2023.03.022. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Rodriguez-Borjabad, Celia; Narverud, Ingunn; Christensen, Jacob J.; Ibarretxe, Daiana; Andreychuk, Natalia & Girona, Josefa [Vis alle 13 forfattere av denne artikkelen] (2023). Association between Nordic and Mediterranean diets with lipoprotein phenotype assessed by ¹HNMR in children with familial hypercholesterolemia. Atherosclerosis. ISSN 0021-9150. 373, s. 38–45. doi: 10.1016/j.atherosclerosis.2023.04.009. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims Both Nordic and Mediterranean diets are considered healthy despite notable regional differences. Although these dietary patterns may lower cardiovascular risk, it is unclear if they improve the lipoprotein phenotype in children with familial hypercholesterolemia (FH). The aim is to determine the impact of Nordic and Mediterranean diets on the advanced lipoprotein profile in children with heterozygous FH (HeFH). Methods This was a cross-sectional study performed in children with FH recruited from the Lipid Clinics at Sant Joan University Hospital in Reus (Spain) and Oslo University Hospital (Norway). Two-hundred fifty-six children (mean age 10 y/o; 48% girls): 85 Spanish and 29 Norwegian FH children, and 142 non-FH healthy controls (119 from Spain and 23 from Norway) were included in the study. A pathogenic FH-associated genetic variant was present in 81% of Spanish children with FH and all Norwegian children with FH. An 1H NMR based advanced lipoprotein test (Nightingale®) providing information on the particle number, size and lipid composition of 14 lipoprotein subclasses was performed and correlated to the dietary components. Results Levels of LDL-C, HDL-C and triglycerides were not significantly different between the Nordic and Mediterranean FH groups. Spanish children with FH had more LDL particles, mainly of the large and medium LDL subclasses, than Norwegian FH children. Spanish FH children also had more HDL particles, mainly medium and small, than Norwegian FH children. The mean LDL size of Spanish FH children was larger, while the HDL size was smaller than that of the Norwegian FH children. The HDL particle number and size were the main determinants of differences between the two groups. In Norwegian children with FH, dietary total fat and MUFAs showed a significant correlation with all apolipoprotein B-containing lipoproteins and LDL size, whereas there was no correlation to SFA. A weaker association pattern was observed in the Spanish children. Conclusions The lipoprotein profiles of Spanish and Norwegian children showed differences when studied by 1H NMR. These differences were in part associated with differences in dietary patterns.

• Rundblad, Amanda; Christensen, Jacob J.; Hustad, Kristin Solheim; Bastani, Nasser Ezzatkhah; Ottestad, Inger & Holven, Kirsten Bjørklund [Vis alle 7 forfattere av denne artikkelen] (2023). Associations between dietary intake and glucose tolerance in clinical and metabolomics-based metabotypes. Genes & Nutrition. ISSN 1555-8932. 18(3). doi: 10.1186/s12263-023-00721-6. Fulltekst i vitenarkiv Vis sammendrag

  Background Metabotyping is a novel concept to group metabolically similar individuals. Different metabotypes may respond differently to dietary interventions; hence, metabotyping may become an important future tool in precision nutrition strategies. However, it is not known if metabotyping based on comprehensive omic data provides more useful identification of metabotypes compared to metabotyping based on only a few clinically relevant metabolites. Aim This study aimed to investigate if associations between habitual dietary intake and glucose tolerance depend on metabotypes identified from standard clinical variables or comprehensive nuclear magnetic resonance (NMR) metabolomics. Methods We used cross-sectional data from participants recruited through advertisements aimed at people at risk of type 2 diabetes mellitus (n = 203). Glucose tolerance was assessed with a 2-h oral glucose tolerance test (OGTT), and habitual dietary intake was recorded with a food frequency questionnaire. Lipoprotein subclasses and various metabolites were quantified with NMR spectroscopy, and plasma carotenoids were quantified using high-performance liquid chromatography. We divided participants into favorable and unfavorable clinical metabotypes based on established cutoffs for HbA1c and fasting and 2-h OGTT glucose. Favorable and unfavorable NMR metabotypes were created using k-means clustering of NMR metabolites. Results While the clinical metabotypes were separated by glycemic variables, the NMR metabotypes were mainly separated by variables related to lipoproteins. A high intake of vegetables was associated with a better glucose tolerance in the unfavorable, but not the favorable clinical metabotype (interaction, p = 0.01). This interaction was confirmed using plasma concentrations of lutein and zeaxanthin, objective biomarkers of vegetable intake. Although non-significantly, the association between glucose tolerance and fiber intake depended on the clinical metabotypes, while the association between glucose tolerance and intake of saturated fatty acids and dietary fat sources depended on the NMR metabotypes. Conclusion Metabotyping may be a useful tool to tailor dietary interventions that will benefit specific groups of individuals. The variables that are used to create metabotypes will affect the association between dietary intake and disease risk.

• Skytte, Hege; Christensen, Jacob J.; Gunnes, Nina; Holven, Kirsten Bjørklund; Lekva, Tove & Henriksen, Tore [Vis alle 8 forfattere av denne artikkelen] (2023). Metabolic profiling of pregnancies complicated by preeclampsia: A longitudinal study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 102(3), s. 334–343. doi: 10.1111/aogs.14505. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Introduction Preeclampsia is associated with maternal metabolic disturbances, but longitudinal studies with comprehensive metabolic profiling are lacking. We aimed to determine metabolic profiles across gestation in women who developed preeclampsia compared with women with healthy pregnancies. We also explored the respective effects of body mass index (BMI) and preeclampsia on various metabolic measures. Material and methods We measured 91 metabolites by high‐throughput nuclear magnetic resonance spectroscopy at four time points (visits) during pregnancy (weeks 14–16, 22–24, 30–32 and 36–38). Samples were taken from a Norwegian pregnancy cohort. We fitted a linear regression model for each metabolic measure to compare women who developed preeclampsia ( n  = 38) and healthy controls ( n  = 70). Results Among women who developed preeclampsia, 92% gave birth after 34 weeks of gestation. Compared to women with healthy pregnancies, women who developed preeclampsia had higher levels of several lipid‐related metabolites at visit 1, whereas fewer differences were observed at visit 2. At visit 3, the pattern from visit 1 reappeared. At visit 4 the differences were larger in most subgroups of very‐low‐density lipoprotein particles, the smallest high‐density lipoprotein, total lipids and triglycerides. Total fatty acids were also increased, of which monounsaturated fatty acids and saturated fatty acids showed more pronounced differences. Concentration of glycine tended to be lower in pregnancies with preeclampsia until visit 3, although this was not significant after correction for multiple testing. After adjustment for age, BMI, parity and gestational weight gain, all significant differences were attenuated at visits 1 and 2. The estimates were less affected by adjustment at visits 3 and 4. Conclusions In early pregnancy, the metabolic differences between preeclamptic and healthy pregnancies were primarily driven by maternal BMI, probably representing the women's pre‐pregnancy metabolic status. In early third trimester, several weeks before clinical manifestation, the differences were less influenced by BMI, indicating preeclampsia‐specific changes. Near term, women with preeclampsia developed an atherogenic metabolic profile, including elevated total lipids, very‐low‐density lipoprotein, triglycerides, and total fatty acids.

• Klevmoen, Marianne; Mulder, Janneke W.C.M.; Lennep, Jeanine E. Roeters van & Holven, Kirsten Bjørklund (2023). Sex Differences in Familial Hypercholesterolemia. Current Atherosclerosis Reports. ISSN 1523-3804. 25, s. 861–868. doi: 10.1007/s11883-023-01155-6. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Purpose of Review This review aims to summarize the existing research on sex differences in familial hypercholesterolemia (FH) across the lifespan. Recent Findings From childhood onward, total- and low-density lipoprotein cholesterol (LDL-C) levels in girls are higher than those in boys with FH. By the age of 30 years, women with FH have a higher LDL-C burden than men. In adulthood, women are diagnosed later than men, receive less lipid-lowering treatment, and consequently have higher LDL-C levels. An excessive atherosclerotic cardiovascular disease risk is reported in young female compared to male FH patients. The periods of pregnancy and breastfeeding contribute to treatment loss and increased cholesterol burden. Summary Earlier initiation of treatment, especially in girls with FH, and lifelong treatment during all life stages are important. Future research should aim to recruit both women and men, report sex-specific data, and investigate the impact of the female life course on cardiovascular outcomes. Future guidelines should include sex-specific aspects. Graphical abstract

• Christensen, Jacob J.; Arnesen, Erik Kristoffer; Rundblad, Amanda; Telle-Hansen, Vibeke; Narverud, Ingunn & Blomhoff, Rune [Vis alle 10 forfattere av denne artikkelen] (2023). Dietary fat quality, plasma atherogenic lipoproteins, and atherosclerotic cardiovascular disease: An overview of the rationale for dietary recommendations for fat intake. Atherosclerosis. ISSN 0021-9150. 389. doi: 10.1016/j.atherosclerosis.2023.117433. Fulltekst i vitenarkiv Vis sammendrag

  The scientific evidence supporting the current dietary recommendations for fat quality keeps accumulating; however, a paradoxical distrust has taken root among many researchers, clinicians, and in parts of the general public. One explanation for this distrust may relate to an incomplete overview of the totality of the evidence for the link between fat quality as a dietary exposure, and health outcomes such as atherosclerotic cardiovascular disease (ASCVD). Therefore, the main aim of the present narrative review was to provide a comprehensive overview of the rationale for dietary recommendations for fat intake, limiting our discussion to ASCVD as outcome. Herein, we provide a core framework – a causal model – that can help us understand the evidence that has accumulated to date, and that can help us understand new evidence that may become available in the future. The causal model for fat quality and ASCVD is comprised of three key research questions (RQs), each of which determine which scientific methods are most appropriate to use, and thereby which lines of evidence that should feed into the causal model. First, we discuss the link between low-density lipoprotein (LDL) particles and ASCVD (RQ1); we draw especially on evidence from genetic studies, randomized controlled trials (RCTs), epidemiology, and mechanistic studies. Second, we explain the link between dietary fat quality and LDL particles (RQ2); we draw especially on metabolic ward studies, controlled trials (randomized and non-randomized), and mechanistic studies. Third, we explain the link between dietary fat quality, LDL particles, and ASCVD (RQ3); we draw especially on RCTs in animals and humans, epidemiology, population-based changes, and experiments of nature. Additionally, the distrust over dietary recommendations for fat quality may partly relate to an unclear understanding of the scientific method, especially as applied in nutrition research, including the process of developing dietary guidelines. We therefore also aimed to clarify this process. We discuss how we assess causality in nutrition research, and how we progress from scientific evidence to providing dietary recommendations.

• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Vis alle 9 forfattere av denne artikkelen] (2022). What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling. NMCD. Nutrition Metabolism and Cardiovascular Diseases. ISSN 0939-4753. 32(7), s. 1651–1660. doi: 10.1016/j.numecd.2022.03.028. Fulltekst i vitenarkiv Vis sammendrag

  Familial hypercholesterolemia (FH) is a genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of pre- mature coronary heart disease (CHD). Cholesterol-lowering therapy (statins) reduces CHD risk, but have been available only in the last 25 years, thus, elderly FH patients have been exposed to elevated LDL-C levels most of their life. Surprisingly, some of these have never experienced any CHD event, raising the question whether they present CHD resistant characteristics. Identifying possible cardioprotective biomarkers could contribute to future CHD preventive treatment, therefore, we aimed to identify metabolic markers in event-free elderly FH subjects. Methods and results: We used a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform to quantify a large number of metabolites in serum samples from 83 FH patients >65 years, and analyze differences between subjects with (n = 39) and without (n = 44) CHD. Mean age was 70 years in both groups (57% and 38% female in the event-free group and CHD group, respectively). The event-free group had significantly higher levels of large and extra-large high-density lipoprotein (HDL) particles, and higher concentration of Apolipoprotein A1 (ApoA1) and cholesterol in HDL and HDL2 particles, compared to the CHD group (p < 0.05 for all). Conclusion: CHD resistant elderly FH patients have higher levels of large HDL particles. The mechanisms behind the event-free survival among these patients remain unclear; hence, a deeper understanding of the metabolic profile in event-free elderly FH subjects may lead to development of novel preventive therapies.

• Christensen, Jacob Juel; Bogsrud, Martin Prøven; Holven, Kirsten Bjørklund; Retterstøl, Kjetil; Veierød, Marit Bragelien & Nordeng, Hedvig Marie Egeland (2022). Use of statins and other lipid-modifying agents across pregnancy: A nationwide drug utilization study in Norway in 2005–2018. Atherosclerosis. ISSN 0021-9150. s. 1–10. doi: 10.1016/j.atherosclerosis.2022.11.022. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims Statins are becoming more widely used among women of reproductive age; however, nationwide data on statin use across pregnancy is scarce. We therefore aimed to describe the drug utilization patterns for statins and other lipid-modifying agents (LMAs) before, during, and after pregnancy, for all pregnancies in Norway from 2005 to 2018. Methods We linked individual-level data from four nationwide electronic health care registries in Norway and characterized the prescription fills of statins and other LMAs across pregnancy. We also examined trends in pregnancy-related LMA use, and characterized women using statins and other LMAs on parameters of health status and co-morbidity. Results In total, 822,071 pregnancies for 503,723 women were included. The number of statin prescription fills decreased rapidly during the first trimester and returned to pre-pregnancy levels about one year postpartum. Pregnancy-related statin use increased from 2005 (approx. 0.11% of all pregnancies) to 2018 (approx. 0.29% of all pregnancies); however, in total, few statin prescriptions were filled within any trimester of pregnancy (n = 331, 0.04% of all pregnancies). Statin use was more common in women with higher age, higher weight, smoking, and comorbidities such as hypertension and diabetes mellitus; also, statin users often had co-medication pertinent to these conditions. Conclusions Although statins and other LMAs were increasingly being used around the time of pregnancy among women in Norway, drug use was mostly discontinued during the first trimester. Our results suggest that pregnancy-related statin use should be monitored, and that drug safety analyses for maternal and offspring health outcomes are needed.

• Christensen, Jacob Juel; Bogsrud, Martin Prøven; Holven, Kirsten Bjørklund; Retterstøl, Kjetil; Veierød, Marit Bragelien & Nordeng, Hedvig Marie Egeland (2022). Use of statins and other lipid-modifying agents across pregnancy – a nationwide drug utilization study of 822 071 pregnancies in Norway in 2005-2018. medRxiv. doi: 10.1101/2022.06.28.22276237. Fulltekst i vitenarkiv
• Pigsborg, Kristina; Gürdeniz, Gözde; Rangel-Huerta, Oscar Daniel; Holven, Kirsten Bjørklund; Dragsted, Lars Ove & Ulven, Stine Marie (2022). Effects of changing from a diet with saturated fat to a diet with n-6 polyunsaturated fat on the serum metabolome in relation to cardiovascular disease risk factors. European Journal of Nutrition. ISSN 1436-6207. 61, s. 2079–2989. doi: 10.1007/s00394-021-02796-6. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Purpose Replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) is associated with a reduced risk of cardiovascular disease. Yet, the changes in the serum metabolome after this replacement is not well known. Therefore, the present study aims to identify the metabolites differentiating diets where six energy percentage SFA is replaced with PUFA and to elucidate the association of dietary metabolites with cardiometabolic risk markers. Methods In an 8-week, double-blind, randomized, controlled trial, 99 moderately hyper-cholesterolemic adults (25–70 years) were assigned to a control diet (C-diet) or an experimental diet (Ex-diet). Both groups received commercially available food items with different fatty acid compositions. In the Ex-diet group, products were given where SFA was replaced mostly with n-6 PUFA. Fasting serum samples were analysed by untargeted ultra-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Pre-processed data were analysed by double cross-validated Partial Least-Squares Discriminant Analysis (PLS-DA) to detect features differentiating the two diet groups. Results PLS-DA differentiated the metabolic profiles of the Ex-diet and the C-diet groups with an area under the curve of 0.83. The Ex-diet group showed higher levels of unsaturated phosphatidylcholine plasmalogens, an unsaturated acylcarnitine, and a secondary bile acid. The C-diet group was characterized by odd-numbered phospholipids and a saturated acylcarnitine. The Principal Component analysis scores of the serum metabolic profiles characterizing the diets were significantly associated with low-density lipoprotein cholesterol, total cholesterol, and triglyceride levels but not with glycaemia. Conclusion The serum metabolic profiles confirmed the compliance of the participants based on their diet-specific metabolome after replacing SFA with mostly n-6 PUFA. The participants' metabolic profiles in response to the change in diet were associated with cardiovascular disease risk markers. This study was registered at clinicaltrials.gov as NCT 01679496 on September 6th 2012.

• Hovland, Anders; Mundal, Liv; Veierød, Marit Bragelien; Holven, Kirsten Bjørklund; Bogsrud, Martin Prøven & Tell, Grethe Seppola [Vis alle 8 forfattere av denne artikkelen] (2022). The risk of various types of cardiovascular diseases in mutation positive familial hypercholesterolemia; a review. Frontiers in Genetics. 13. doi: 10.3389/fgene.2022.1072108. Fulltekst i vitenarkiv Vis sammendrag

  Familial hypercholesterolemia (FH) is a common, inherited disease characterized by high levels of low-density lipoprotein Cholesterol (LDL-C) from birth. Any diseases associated with increased LDL-C levels including atherosclerotic cardiovascular diseases (ASCVDs) would be expected to be overrepresented among FH patients. There are several clinical scoring systems aiming to diagnose FH, however; most individuals who meet the clinical criteria for a FH diagnosis do not have a mutation causing FH. In this review, we aim to summarize the literature on the risk for the various forms of ASCVD in subjects with a proven FH-mutation (FH+). We searched for studies on FH+ and cardiovascular diseases and also included our and other groups published papers on FH + on a wide range of cardiovascular and other diseases of the heart and vessels. FH + patients are at a markedly increased risk of a broad range of ASCVD. Acute myocardial infarction (AMI) is the most common in absolute numbers, but also aortic valve stenosis is by far associated with the highest excess risk. Per thousand patients, we observed 3.6 incident AMI per year compared to 1.9 incident aortic valve stenosis, however, standardized incidence ratio (SIR) for incident AMI was 2.3 compared to 7.9 for incident aortic valve stenosis. Further, occurrence of ischemic stroke seems not to be associated with increased risk in FH+. Clinicians should be aware of the excess risk of almost all kind of ASCVD in FH+, and the neutral risk of stroke need to be studied further in FH + patients.

• Parys, Anthea van; Sæle, Jostein; Puaschitz, Nathalie Genevieve; Anfinsen, Åslaug Matre; Karlsson, Therese & Olsen, Thomas [Vis alle 12 forfattere av denne artikkelen] (2022). The association between dairy intake and risk of cardiovascular disease and mortality in patients with stable angina pectoris. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 30(3), s. 219–229. doi: 10.1093/eurjpc/zwac217. Fulltekst i vitenarkiv Vis sammendrag

  Aims The association of dairy products with cardiovascular disease and mortality risk remains heavily debated. We aimed to investigate the association between intake of total dairy and dairy products and the risk of acute myocardial infarction (AMI), stroke, and cardiovascular and all-cause mortality. Methods and results We included 1929 patients (80% men, mean age 62 years) with stable angina pectoris from the Western Norway B-vitamin Intervention Trial. Dietary data were obtained via a 169-item food frequency questionnaire. Risk associations were estimated using Cox proportional hazard regression models adjusted for relevant covariates. Non-linear associations were explored visually. The mean (±SD) dairy intake in the study population was 169 ± 108 g/1000 kcal. Median follow-up times were 5.2, 7.8, and 14.1 years for stroke, AMI, and mortality, respectively. Higher intake of total dairy and milk were positively associated with stroke risk [HR (95% CI): 1.14 (1.02, 1.27) and 1.13 (1.02, 1.27), cardiovascular mortality 1.06 (1.00, 1.12) and 1.07 (1.01, 1.13)] and all-cause mortality [1.07 (1.03, 1.11) and 1.06 (1.03, 1.10)] per 50 g/1000 kcal. Higher cheese intake was inversely associated with AMI risk [0.92 (0.83, 1.02)] per 10 g/1000 kcal. Butter was associated with increased AMI risk [1.10 (0.97, 1.24)] and all-cause mortality [1.10 (1.00, 1.20) per 5 g/1000 kcal. Conclusion Higher dairy and milk consumption were associated with increased risk of mortality and stroke. Cheese was associated with decreased, and butter with increased, risk of AMI. Dairy is a heterogenous food group with divergent health effects and dairy products should therefore be investigated individually.

• Hustad, Kristin Solheim; Ottestad, Inger; Olsen, Thomas; Sæther, Thomas; Ulven, Stine Marie & Holven, Kirsten Bjørklund (2022). Salmon fish protein supplement increases serum vitamin B12 and selenium concentrations: secondary analysis of a randomised controlled trial. European Journal of Nutrition. ISSN 1436-6207. 61(6), s. 3085–3093. doi: 10.1007/s00394-022-02857-4. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Purpose The main aim of the present study was to examine the effect of a fish protein supplement made from by-products from production of Atlantic salmon, on blood concentration of micronutrients. Methods We conducted an 8-week double-blind parallel-group randomised controlled trial. In total, 88 adults were randomised to a salmon fish protein supplement or placebo, and 74 participants were included in the analysis of vitamin D, omega-3, vitamin B12, selenium, folate, zinc, homocysteine and mercury. Results During the intervention period, geometric mean (GSD) of serum vitamin B12 concentrations increased from 304 (1.40) to 359 (1.42) pmol/L in the fish protein group ( P vs. controls = 0.004) and mean (SD) serum selenium increased from 1.18 (0.22) to 1.30 (0.20) μmol/L ( P vs. controls = 0.002). The prevalence of low vitamin B12 status (B12 &lt; 148–221 &gt; pmol/L) decreased from 15.4 to 2.6% in the fish protein group, while increasing from 5.9 to 17.6% in the placebo group ( P  = 0.045). There was no difference between the groups in serum levels of the other micronutrients measured. Conclusion Including a salmon fish protein supplement in the daily diet for 8 weeks, increases serum vitamin B12 and selenium concentrations. From a sustainability perspective, by-products with high contents of micronutrients and low contents of contaminants, could be a valuable dietary supplement or food ingredient in populations with suboptimal intake. Trail Registration The study was registered at ClinicalTrials.gov (ID: NCT03764423) on June 29th 2018.

Se alle arbeider i NVA

• Khalil, Youssef Samir Abouzeid Mohamed; Vesterbekkmo, Elisabeth Kleivhaug; Holven, Kirsten Bjørklund; Dalen, Håvard; Retterstøl, Kjetil & Blom, Sigrid Marie [Vis alle 8 forfattere av denne artikkelen] (2026). LIPOPROTEIN(A), AGE AND SEX-SPECIFIC ABSOLUTE AND RELATIVE HAZARDS OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE: NEW INSIGHTS FROM 16-YEAR FOLLOW-UP OF THE NORWEGIAN HUNT STUDY. Atherosclerosis. ISSN 0021-9150. 419, s. 121083–121083. doi: 10.1016/j.atherosclerosis.2026.121083. Fulltekst i vitenarkiv Vis sammendrag

  Background and Aims: Atherosclerotic cardiovascular disease (ASCVD) develops through cumulative exposure to causal risk factors, such as lipoprotein(a) [Lp(a)]. Evidence on how high Lp(a) shapes long-term absolute and relative ASCVD hazards across age and sex remains limited. We quantified age and sex-specific absolute and relative ASCVD hazards associated with high Lp(a) and assessed whether these age-related patterns differed between men and women. Methods: We included 19 495 adults without ASCVD at baseline with Lp(a) measured from the Trøndelag Health Study (HUNT3, 2006–08). Participants were followed for up to 16 years for first ASCVD event. Lp(a) was categorized as high (≥95th percentile; ≥252 nmol/L) versus low (≤74th percentile; ≤62 nmol/L). Standardized age and sex-specific hazard rates, hazard ratios (HRs), and hazard rate differences (HRDs) per 1000 person-years were estimated using multivariable cause-specific flexible parametric survival models. Results: High Lp(a) was associated with higher ASCVD hazards at all ages. In both sexes combined, the HR for high versus low Lp(a) declined from 2.42 (95% CI: 1.14–5.14) at age 40 to 1.24 (95% CI: 0.91–1.70) at age 90, while corresponding HRDs increased from 1.22 (95% CI: -0.24–2.67) to 6.97 (95% CI: -4.08–18.02) extra ASCVD events per 1000 person-years. Men had higher ASCVD hazards than women at all ages. HRs were broadly similar between sexes but tended to be slightly higher in women at midlife. However, the number of extra ASCVD events per 1000 person-years due to high Lp(a) increased with age in both sexes and was consistently higher in men compared to women. Conclusions: High Lp(a) is a long-term risk factor for ASCVD across adulthood, with a larger relative impact at younger ages, but causes more excess events in older adults, and particularly in men. These risk profiles may help clinicians prioritize Lp(a) testing and identify patients who may benefit from future Lp(a)-lowering therapies.

• Klevmoen, Marianne; Mulder, Janneke W.C.M.; Bogsrud, Martin Prøven; Retterstøl, Kjetil; Vesterbekkmo, Elisabeth Kleivhaug & Pedersen, Eva Ringdal [Vis alle 16 forfattere av denne artikkelen] (2025). Prospective study on breastfeeding, lipid profile and cardiovascular risk markers in women with familial hypercholesterolaemia: study protocol for the FH-FEMINA study. doi: 10.1136/bmjopen-2024-092208. Fulltekst i vitenarkiv
• Lennep, Jeanine E. Roeters van; Öörni, Katariina; Binder, Christoph J.; Kronenberg, Florian; Mallat, Ziad & Raggi, Paolo [Vis alle 15 forfattere av denne artikkelen] (2025). The essential role of sex and gender in atherosclerosis research: A statement from the Editorial Board of Atherosclerosis and Executive Committee of the European Atherosclerosis Society. Atherosclerosis. ISSN 0021-9150. 407. doi: 10.1016/j.atherosclerosis.2025.120403. Fulltekst i vitenarkiv
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Rasmussen, Kathleen M; Winkvist, Anna; Løland, Beate Fossum & Holven, Kirsten Bjørklund [Vis alle 7 forfattere av denne artikkelen] (2025). Post-weaning results from a Randomized Controlled Trial on Weight and Cardiometabolic Risk Factors - Effects of Breastfeeding Promotion Intervention and Dietary Treatment in Postpartum Women with Overweight and Obesity. Fulltekst i vitenarkiv Vis sammendrag

  Foredrag på International Conference of Nutrition (ICN)

• Øhman, Elisabeth Adolfsen; Fossli, Maria; Rasmussen, Kathleen M.; Winkvist, Anna; Løland, Beate Fossum & Holven, Kirsten Bjørklund [Vis alle 7 forfattere av denne artikkelen] (2025). Effects of breastfeeding and diet interventions in postpartum women with overweight and obesity: Results from an RCT on weight and cardiometabolic risk factors. Fulltekst i vitenarkiv Vis sammendrag

  Foredrag på Throne Holst seminar

• Fossli, Maria; Øhman, Elisabeth Adolfsen; Rasmussen, Kathleen M.; Winkvist, Anna; Løland, Beate Fossum & Holven, Kirsten Bjørklund [Vis alle 7 forfattere av denne artikkelen] (2025). Effekter av ammeintervensjon og kostintervensjon hos postpartum kvinner med overvekt og fedme: Resultater fra en randomisert, kontrollert studie på vekt og kardiometabolske risikofaktorer. Fulltekst i vitenarkiv
• Mulder, Janneke W. C. M.; Pang, Jing; Klevmoen, Marianne; Kranenburg, Leonieke W.; Retterstøl, Kjetil & Boersma, Eric [Vis alle 9 forfattere av denne artikkelen] (2025). Family planning, pregnancy, and breastfeeding care in familial hypercholesterolaemia: A study protocol for a mixed-methods study in the Netherlands, Norway and Australia (Taking ACTion to Improve Care of coupleS in FH (TACTICS)). doi: 10.1136/bmjopen-2024-089187. Fulltekst i vitenarkiv
• Uduma, Amara Synøve; Sverre, Elise Christine Bjørkholen; Munkhaugen, John; Retterstøl, Kjetil; Bogsrud, Martin Prøven & Holven, Kirsten Bjørklund [Vis alle 7 forfattere av denne artikkelen] (2025). More musculoskeletal disorders and poor pain management in patients with familial hypercholesterolemia and self-perceived side effects to cholesterol-lowering treatment. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: To compare clinical and psychosocial characteristics of patients with FH, with and without self-perceived side effects to cholesterol-lowering treatment. Methods: A group of 929 adult outpatients with confirmed genetic FH from a regional treatment register in Norway were invited to an observational study. The participants completed a digital questionnaire covering self-perceived side effects (any symptoms), use of cholesterol-lowering medications, musculoskeletal disorders or rheumatic diseases, and muscular symptoms and pain treatment. We collected data on FH diagnosis, comorbidities, and biomarkers in blood from the last consultation listed in the treatment register. Results: Mean age was 52 (SD 15) years, and 57% were women. Thirty-eight (15%) out of 255 participants reported self-perceived side effects to cholesterol-lowering treatment. Patients with self-perceived side effects were more frequently living alone (26% vs. 12%, p=0.025) and had slightly higher LDL-C than those without side effects, whereas no differences in creatine kinase or alanine transaminase were observed. Patients with self-perceived side effects had a higher frequency of musculoskeletal disorders or rheumatic diseases (58% vs. 37%, p<0.001) than those with no side effects (Table 1). They also reported more muscle symptoms the last month in general, and specifically from the hips, thighs, calves, shoulders, and neck. Median pain intensity the last 24-hours was significantly higher (3 vs. 1 on a 0 [no] to 10 [worst imaginable] numeric rating scale, p<0.001) in patients with side effects, and 58% currently used no pain medication (Table 2). Conclusions: Patients with FH and self-perceived side effects frequently have musculoskeletal disorders or rheumatic diseases and clinically significant pain without treatment. Our study suggests that a considerable proportion of patients misattribute muscle symptoms and pain to their cholesterol-lowering medications. Future work should focus on musculoskeletal- and rheumatic conditions as an alternative explanation for self-perceived side effects to cholesterol-lowering medication.

• Øhman, Elisabeth Adolfsen; Fossli, Maria; Rasmussen, Kathleen M.; Winkvist, Anna; Løland, Beate Fossum & Holven, Kirsten Bjørklund [Vis alle 7 forfattere av denne artikkelen] (2024). Effekter av ammeintervensjon og kostintervensjon hos postpartum kvinner med overvekt og fedme: Resultater fra en randomisert, kontrollert studie på vekt og kardiometabolske risikofaktorer. Fulltekst i vitenarkiv
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Rasmussen, Kathleen M.; Winkvist, Anna; Løland, Beate Fossum & Holven, Kirsten Bjørklund [Vis alle 7 forfattere av denne artikkelen] (2024). Effekter av ammeintervensjon og kostintervensjon hos postpartum kvinner med overvekt og fedme: Resultater fra en randomisert, kontrollert studie på vekt og kardiometabolske risikofaktorer. Fulltekst i vitenarkiv
• Brekke, Hilde Kristin; Fossli, Maria; Rasmussen, Kathleen; Winkvist, Anna; Holven, Kirsten Bjørklund & Løland, Beate Fossum (2024). Effekter av ammeintervensjon og kostintervensjon hos postpartum kvinner med overvekt og fedme: Resultater fra en randomisert, kontrollert studie på vekt og kardiometabolske risikofaktorer. Fulltekst i vitenarkiv
• Fossli, Maria; Øhman, Elisabeth Adolfsen; Andal, Malin; Løland, Beate Fossum; Holven, Kirsten Bjørklund & Brekke, Hilde Kristin (2024). Nutrient intake among lactating women with overweight and obesity. Fulltekst i vitenarkiv
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Rasmussen, Kathleen M.; Winkvist, Anna; Løland, Beate Fossum & Holven, Kirsten Bjørklund [Vis alle 7 forfattere av denne artikkelen] (2024). Effects of breastfeeding and diet interventions in postpartum women with overweight and obesity: Results from an RCT on weight and cardiometabolic risk factors. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. 22(5). Fulltekst i vitenarkiv
• Fossli, Maria; Øhman, Elisabeth Adolfsen; Andal, Malin; Løland, Beate Fossum; Holven, Kirsten Bjørklund & Brekke, Hilde Kristin (2024). Nutrient intake among lactating women with overweight and obesity. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. 22(5). Fulltekst i vitenarkiv
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Rasmussen, Kathleen M.; Winkvist, Anna; Løland, Beate Fossum & Holven, Kirsten Bjørklund [Vis alle 7 forfattere av denne artikkelen] (2024). Effects of breastfeeding and diet interventions in postpartum women with overweight and obesity: Results from an RCT on weight and cardiometabolic risk factors. Fulltekst i vitenarkiv
• Fossli, Maria; Øhman, Elisabeth Adolfsen; Andal, Malin; Løland, Beate Fossum; Holven, Kirsten Bjørklund & Brekke, Hilde Kristin (2024). Inntak av næringsstoffer blant ammende kvinner med overvekt og fedme. Fulltekst i vitenarkiv
• Fossli, Maria; Øhman, Elisabeth Adolfsen; Andal, Malin; Løland, Beate Fossum; Holven, Kirsten Bjørklund & Brekke, Hilde Kristin (2024). Dietary intake among lactating women with overweight and obesity at seven weeks postpartum. Fulltekst i vitenarkiv
• Fossli, Maria; Brekke, Hilde Kristin; Rasmussen, Kathleen M.; Winkvist, Anna; Løland, Beate Fossum & Holven, Kirsten Bjørklund (2024). Effekter av ammeintervensjon og kostintervensjon hos postpartum kvinner med overvekt og fedme: Resultater fra en randomisert, kontrollert studie på vekt og kardiometabolske risikofaktorer. Fulltekst i vitenarkiv
• Fossli, Maria; Brekke, Hilde Kristin; Rasmussen, Kathleen M.; Winkvist, Anna; Løland, Beate Fossum & Holven, Kirsten Bjørklund (2024). Effekter av ammeintervensjon og kostintervensjon hos postpartum kvinner med overvekt og fedme: Resultater fra en randomisert, kontrollert studie på vekt og kardiometabolske risikofaktorer. Fulltekst i vitenarkiv
• Fossli, Maria; Øhman, Elisabeth Adolfsen; Andal, Malin; Løland, Beate Fossum; Holven, Kirsten Bjørklund & Brekke, Hilde Kristin (2024). Nutrient Intake among lactating women with overweight and obesity. Fulltekst i vitenarkiv
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger Olaug; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Vis alle 7 forfattere av denne artikkelen] (2024). Dietary treatment postpartum in women with obesity reduces weight and prevents weight gain: a randomised controlled trial. Fulltekst i vitenarkiv
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Vis alle 7 forfattere av denne artikkelen] (2023). Effect of a postpartum weight loss intervention in women with obesity: a randomized controlled trial. Fulltekst i vitenarkiv
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Vis alle 7 forfattere av denne artikkelen] (2023). Kostprogram postpartum reduserer vekt og forebygger vektoppgang blant kvinner med fedme – en randomisert kontrollert studie. Fulltekst i vitenarkiv
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Vis alle 10 forfattere av denne artikkelen] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Fulltekst i vitenarkiv
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Vis alle 10 forfattere av denne artikkelen] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Fulltekst i vitenarkiv
• Holven, Kirsten Bjørklund (2023). Plasma cholesterol levels in infancy: a neglected resource. European Heart Journal. ISSN 0195-668X. 44(42), s. 4419–4421. doi: 10.1093/eurheartj/ehad558. Fulltekst i vitenarkiv
• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Vis alle 9 forfattere av denne artikkelen] (2023). What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling. Fulltekst i vitenarkiv
• Rundblad, Amanda; Hansen, Anna Lena; Christensen, Jacob Juel; Melnes, Torunn; Ottestad, Inger Olaug & Narverud, Ingunn [Vis alle 12 forfattere av denne artikkelen] (2023). Patients with familial hypercholesterolemia have shorter telomeres than controls in older, but not in young subjects: a cross-sectional study. Fulltekst i vitenarkiv
• Rundblad, Amanda; Christensen, Jacob Juel; Hustad, Kristin Solheim; Bastani, Nasser Ezzatkhah; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2023). Associations between dietary intake and glucose tolerance in  clinical and metabolomics-based metabotypes. Fulltekst i vitenarkiv
• Rundblad, Amanda; Das, Siddhartha; Matthews, Jason; Ginos, Gina; Kavousi, Maryam & Holven, Kirsten Bjørklund [Vis alle 7 forfattere av denne artikkelen] (2023). Air pollution, built environment and associations with gene expression and CVD risk markers in adults. Fulltekst i vitenarkiv
• Ulven, Stine Marie; Ottestad, Inger Olaug; Christensen, Jacob Juel & Holven, Kirsten Bjørklund (2023). Inflammatory markers and frailty in home-dwelling elderly, a cross-sectional study. Fulltekst i vitenarkiv
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Vis alle 7 forfattere av denne artikkelen] (2023). Effect of a postpartum weight loss intervention in women with obesity: a randomized controlled trial. Fulltekst i vitenarkiv
• Ueland, Thor; Äikäs, Lauri A.O.; Dahl, Tuva Børresdatter; Gregersen, Ida; Olsen, Maria Belland & Michelsen, Annika Elisabet [Vis alle 20 forfattere av denne artikkelen] (2023). Low-density lipoprotein particles carrying proinflammatory proteins with altered aggregation pattern detected in COVID-19 patients 3 months after hospitalization. Journal of Infection. ISSN 0163-4453. 86(5), s. 489–492. doi: 10.1016/j.jinf.2023.02.024. Fulltekst i vitenarkiv
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Vis alle 10 forfattere av denne artikkelen] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Fulltekst i vitenarkiv
• Troensegaard, Hannibal; Khoury, Janette; Westerberg, Ane Cecilie; Tonstad, Serena; Lennep, Jeanine Roeters van & Veierød, Marit Bragelien [Vis alle 9 forfattere av denne artikkelen] (2023). Protocol for a 20-year follow-up after a randomized controlled trial of a Mediterranean diet in pregnancy: maternal and offspring risk factors for cardiovascular disease. Frontiers in Pediatrics. 11. doi: 10.3389/fped.2023.1256815. Fulltekst i vitenarkiv Vis sammendrag

  Background: An inadequate maternal diet during pregnancy can impair offspring health and may increase the risk of cardiovascular disease later in life. The purpose of the proposed study is to assess the risk factors associated with cardiovascular disease in both mothers and their offspring 20 years following their participation in a Mediterranean diet intervention trial during pregnancy. Methods: The “Cardiovascular Risk Reduction Diet In Pregnancy” (CARRDIP) study was a randomized controlled trial performed between 1999 and 2001. The participants were randomized to adhere to either a Mediterranean diet or their regular diet during pregnancy. An extensive amount of data such as diet information, ultrasound measurements, anthropometry, and biomarkers from these mothers during pregnancy and their offspring in the neonatal period were collected. The mother–offspring pairs (n = 269) from the CARRDIP study will be invited to participate in a clinical examination and blood sample collection. This follow-up study, conducted 20 years after the original CARRDIP study, will investigate cardiovascular risk factors in mothers and offspring. The primary outcome will be the blood pressure of the offspring. In addition, the study will explore various aspects of cardiovascular health, including metabolic and inflammatory status, clinical history, and body composition of the participants. Discussion: Previous studies investigating the effects of nutrition during pregnancy on maternal and offspring health have been either observational studies, animal studies, or randomized controlled trials with a follow-up period of less than 5 years. This project aims to study the long-term effects of dietary intervention during pregnancy on maternal and offspring cardiovascular risk markers.

• Holven, Kirsten Bjørklund; Ulven, Stine Marie; Ottestad, Inger Olaug & Christensen, Jacob Juel (2023). Inflammatory markers and frailty markers in home-dwelling elderly, a cross-sectional study. Fulltekst i vitenarkiv
• Holven, Kirsten Bjørklund; Ulven, Stine Marie; Christensen, Jacob Juel & Ottestad, Inger Olaug (2023). Betydning av kosten for endring i skrøpelighet hos hjemmeboende eldre etter 8 års oppfølging. Fulltekst i vitenarkiv
• Mundal, Liv; Igland, Jannicke; Svendsen, Karianne; Holven, Kirsten Bjørklund; Leren, Trond Paul & Retterstøl, Kjetil (2022). No excess risk of dementia in individuals with familial hypercholesterolemia compared with age and sex matched controls. Fulltekst i vitenarkiv
• Svendsen, Karianne; Mundal, Liv; Holven, Kirsten Bjørklund; Igland, Jannicke; Bogsrud, Martin Prøven & Leren, Trond Paul [Vis alle 7 forfattere av denne artikkelen] (2022). Diseases occuring frequently in a “genetic high LDL-cholesterol (LDL-C) model disease” may be caused by LDL-C itself, or by the treatment of a high LDL-C. Fulltekst i vitenarkiv
• Svendsen, Karianne; Urke, Eli Bjørnøy; Igland, Jannicke; Mundal, Liv; Holven, Kirsten Bjørklund & Retterstøl, Kjetil (2022). Can disease-related diet treatment from childhood result in eating disorders in adulthood? Fulltekst i vitenarkiv
• Klevmoen, Marianne; Bogsrud, Martin Prøven; Retterstøl, Kjetil; Svilaas, Tone; Vesterbekkmo, Elisabeth Kleivhaug & Hovland, Anders Wilhelm [Vis alle 9 forfattere av denne artikkelen] (2022). Loss of statin treatment years during pregnancy and breastfeeding periods in women with familial hypercholesterolemia. Fulltekst i vitenarkiv
• Øhman, Elisabeth Adolfsen; Brekke, Hilde Kristin & Holven, Kirsten Bjørklund (2024). Weight and cardiometabolic risk factors in postpartum women with overweight and obesity - Results from three randomised controlled trials. Universitetet i Oslo. Fulltekst i vitenarkiv Vis sammendrag

  After childbirth, both an increase in weight and a lower level of the "good" HDL cholesterol (HDL-C) may be mechanisms contributing to elevated maternal risk for cardiovascular disease (CVD) and type 2 diabetes (T2D). Weight loss in adults with overweight and obesity has been shown to increase HDL-C. Breastfeeding is associated to a more favourable risk profile for CVD and T2D, including a higher level of HDL-C, while it is more uncertain whether breastfeeding also contributes to weight loss. The aim of the thesis was to examine the effects of a dietary intervention, an exercise treatment, and a breastfeeding promotion intervention (BPI) in postpartum women with overweight and obesity. A Swedish randomised controlled trial (RCT), the LEVA study, showed that lactating women with overweight and obesity before pregnancy lost 9% of their weight and improved their HDL-C and fasting insulin levels through a 12-week dietary program from 3 to 6 months after childbirth. A secondary analysis of the LEVA study showed that the dietary program changed the distribution of HDL particle subclasses in a direction associated with lower risk of CVD. An exercise intervention, which showed no effect on weight, had a more limited effect on the HDL subclasses than the dietary program. In a second RCT, the dietary program was tested in women postpartum with a higher body mass index than in the LEVA study. The program had a positive effect also among these women by reducing weight or preventing weight gain. In a third RCT, the effects of a BPI and the dietary program were examined among postpartum women with overweight and obesity. At 6 months postpartum, almost all participants were breastfeeding. There were no effects of BPI, while the dietary program resulted in a reduction of weight and fasting glucose. In summary, the dietary program led to weight reduction and other favourable effects on risk factors for HKS and T2D, which may improve the mothers' future health.

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