21 results on '"Martin P. Bogsrud"'
Search Results
2. Timing of cardioverter-defibrillator implantation in patients with cardiac laminopathies—External validation of the LMNA-risk ventricular tachyarrhythmia calculator
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Christine Rootwelt-Norberg, Alex Hørby Christensen, Eystein T. Skjølsvik, Monica Chivulescu, Christoffer R. Vissing, Henning Bundgaard, Eivind W. Aabel, Martin P. Bogsrud, Nina E. Hasselberg, Øyvind H. Lie, and Kristina H. Haugaa
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Lamin A/C ,LMNA cardiomyopathy ,Laminopathy ,Physiology (medical) ,Primary preventive ICD ,LMNA-risk VTA calculator ,Cardiology and Cardiovascular Medicine ,Ventricular tachyarrhythmia - Abstract
Background: LMNA genotype-positive patients have high risk of experiencing life-threatening ventricular tachyarrhythmias (VTAs). The LMNA-risk VTA calculator published in 2019 has not been externally validated. Objective: The purpose of this study was to validate the LMNA-risk VTA calculator. Methods: We included LMNA genotype-positive patients without previous VTAs from 2 large Scandinavian centers. Patients underwent electrocardiography, 24-hour Holter monitoring, and echocardiographic examinations at baseline and repeatedly during follow-up. Validation of the LMNA-risk VTA calculator was performed using Harrell's C-statistic derived from multivariable Cox regression analysis. Results: We included 118 patients (age 37 years [IQR 27–49 years]; 39 [33%] probands; 65 [55%] women; 100 [85%] with non-missense LMNA variants). Twenty-three patients (19%) experienced VTA during 6.1 years (interquartile range 3.0–9.1 years) follow-up, resulting in 3.0% (95% confidence interval 2.0%–4.5%) yearly incidence rate. Atrioventricular block and reduced left ventricular ejection fraction were independent predictors of VTAs, while nonsustained ventricular tachycardia, male sex, and non-missense LMNA variants were not. The LMNA-risk VTA calculator showed 83% sensitivity and 26% specificity for identifying patients with VTAs during the coming 5 years, and a Harrell's C-statistic of 0.85, when applying ≥7% predicted 5-year VTA risk as threshold. The sensitivity increased to 100% when reevaluating risk at the time of last consultation before VTA. The calculator overestimated arrhythmic risk in patients with mild and moderate phenotype, particularly in men. Conclusion: Validation of the LMNA-risk VTA calculator showed high sensitivity for subsequent VTAs, but overestimated arrhythmic risk when using ≥7% predicted 5-year risk as threshold. Frequent reevaluation of risk was necessary to maintain the sensitivity of the model.
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- 2023
3. Differential effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) and fatty acids
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Kirsten A, Berk, Heidi, Borgeraas, Ingunn, Narverud, Monique T, Mulder, Linn K L, Øyri, Adrie J M, Verhoeven, Milada Cvancarova, Småstuen, Martin P, Bogsrud, Torbjørn, Omland, Jens Kristoffer, Hertel, Espen, Gjevestad, Njord, Nordstrand, Kirsten B, Holven, and Jøran, Hjelmesæth
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Arachidonic Acid ,Treatment Outcome ,Fatty Acids ,Weight Loss ,Humans ,Bariatric Surgery ,Obesity ,Life Style ,Lipoprotein(a) ,Obesity, Morbid - Abstract
Limited evidence suggests that surgical and non-surgical obesity treatment differentially influence plasma Lipoprotein (a) [Lp(a)] levels. Further, a novel association between plasma arachidonic acid and Lp(a) has recently been shown, suggesting that fatty acids are a possible target to influence Lp(a). Here, the effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) were compared, and it was examined whether the effects were mediated by changes in plasma fatty acid (FA) levels.The study includes two independent trials of patients with overweight or obesity. Trial 1: Two-armed intervention study including 82 patients who underwent a 7-week low energy diet (LED), followed by Roux-en-Y gastric bypass and 52-week follow-up (surgery-group), and 77 patients who underwent a 59-week energy restricted diet- and exercise-program (lifestyle-group). Trial 2: A clinical study including 134 patients who underwent a 20-week very-LED/LED (lifestyle-cohort).In the surgery-group, Lp(a) levels [median (interquartile range)] tended to increase in the pre-surgical LED-phase [17(7-68)-21(7-81)nmol/L, P = 0.05], but decreased by 48% after surgery [21(7-81)-11(7-56)nmol/L, P 0.001]. In the lifestyle-group and lifestyle-cohort, Lp(a) increased by 36%[14(7-77)-19(7-94)nmol/L, P 0.001] and 14%[50(14-160)-57(19-208)nmol/L, P 0.001], respectively. Changes in Lp(a) were independent of weight loss. Plasma levels of total saturated FAs remained unchanged after surgery, but decreased after lifestyle interventions. Arachidonic acid and total n-3 FAs decreased after surgery, but increased after lifestyle interventions. Plasma FAs did not mediate the effects on Lp(a).Bariatric surgery reduced, whereas lifestyle interventions increased plasma Lp(a), independent of weight loss. The interventions differentially influenced changes in plasma FAs, but these changes did not mediate changes in Lp(a).Trial 1: Clinicaltrials.gov NCT00626964. Trial 2: Netherlands Trial Register NL2140 (NTR2264).
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- 2022
4. Treatment goals in familial hypercholesterolaemia—time to consider low-density lipoprotein-cholesterol burden
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Gisle Langslet, Kirsten B Holven, and Martin P Bogsrud
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Hyperlipoproteinemia Type II ,Epidemiology ,Humans ,Cholesterol, LDL ,Cardiology and Cardiovascular Medicine - Published
- 2021
5. Use of statins and other lipid-modifying agents across pregnancy: A nationwide drug utilization study in Norway in 2005–2018
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Jacob J. Christensen, Martin P. Bogsrud, Kirsten B. Holven, Kjetil Retterstøl, Marit B. Veierød, and Hedvig Nordeng
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Cardiology and Cardiovascular Medicine - Abstract
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.
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- 2022
6. Risk of stroke in genetically verified familial hypercholesterolemia: A prospective matched cohort study
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Karianne Svendsen, Thomas Olsen, Kathrine J. Vinknes, Liv J. Mundal, Kirsten B. Holven, Martin P. Bogsrud, Trond P. Leren, Jannicke Igland, and Kjetil Retterstøl
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Cohort Studies ,Hyperlipoproteinemia Type II ,Stroke ,Hemorrhagic Stroke ,Fibrinolytic Agents ,Risk Factors ,Humans ,Cholesterol, LDL ,Prospective Studies ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,Ischemic Stroke - Abstract
Background and aims Individuals with familial hypercholesterolemia (FH), causing severely elevated LDL-C, are expected to have a higher risk of ischemic stroke. The risk of hemorrhagic stroke and impact of statin use are, however, not known. We aimed to investigate the risk of incident total, ischemic and hemorrhagic stroke in individuals with FH compared to controls, and to explore the association between cumulative statin use and risk of total stroke in FH. Methods This prospective cohort study consists of 4186 individuals with genetically verified FH and 82 180 age and sex matched controls followed from 2008 to 2018 for incident stroke. Daily defined doses (DDD) described cumulative statin exposure: 0–5000 DDD (“low”), 5000–10,000 DDD (“intermediate”), and >10 000 DDD (“high”). Results were presented as hazard ratio (95% CI) derived from Cox proportional hazards models. Results Individuals with FH did not have a higher risk of total stroke (1.16 (0.95–1.43) nor ischemic stroke (1.11 (0.88–1.38). Excess risk of hemorrhagic stroke was observed (1.63 (1.07, 2.48) but attenuated after adjusting for antithrombotic medication (1.25 (0.81, 1.93). Among individuals with FH, there was no association between statin use and total stroke for intermediate vs. low DDD [0.69 (0.32, 1.48)] or for high vs. low DDD [0.83 (0.41, 1.67)]. Conclusions No significant excess risk of incident total and ischemic stroke in FH, and no difference in total stroke risk among the FH population with low, intermediate, and high statin exposure were observed. The observed relationship between FH and hemorrhagic stroke was no longer significant after adjusting for use of anti-thrombotic medication. publishedVersion
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- 2022
7. Abstract 15749: Sex-differences in Coronary Heart Disease Between Individuals With Familial Hypercholesterolemia and Controls in Norway During 1992-2017
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Karianne Svendsen, Kirsten B. Holven, Kjetil Retterstøl, Trond P. Leren, Henriette Walaas Krogh, Martin P. Bogsrud, Jannicke Igland, Liv Mundal, and Grethe S. Tell
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medicine.medical_specialty ,business.industry ,Physiology (medical) ,Internal medicine ,medicine ,Familial hypercholesterolemia ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business ,Coronary heart disease - Abstract
Introduction: During the last 30 years, treatment of familial hypercholesterolemia (FH) has been revolutionized, but it is not known if both sexes equally benefit in these advances, and whether this could have affected the sex difference in risk of coronary heart disease (CHD). We aimed to study sex difference in the risk of CHD between men and women with FH compared to non-FH men and women. Methods: We obtained data on CHD hospitalization and death from Norwegian health registries in 4,525 individuals diagnosed with FH between 1992 and 2014 and an age and sex matched control population of 88,892. The sex distribution was about 50/50 between women and men, and the mean age at start of follow-up was 36 years. Results: The cumulative incidence of CHD (FH vs. non-FH controls) in women and men are shown in Figure 1 with a clear increased risk in FH compared to controls. The cumulative incidence starts to increase at a younger age in men compared with women, both in FH and non-FH controls. This corresponds to an age adjusted 2.6-fold higher risk of CHD in men compared with women in both the FH and control population. In the FH population, men aged 20-39 years had a hazard ratio (HR) of 5.3 (95% CI: 2.6-10.9) compared with women, whereas the corresponding HR between women and men in non-FH controls was 3.7 (95% CI: 2.6-5.3). There was no significant interaction between sex and FH status, indicating that the excess risk in men was similar in FH and non-FH controls. Stratified by sex and adjusted for age, we found that both men and women with FH had a 2-fold higher risk of CHD than controls. The highest excess risk was observed in ages 20-30 years with a of HR= 4.5 (95% CI: 2.2-9.2) and a HR of= 5.5 (95%CI: 4.60-9.34) in women and men, respectively. Conclusions: The risk of CHD among individuals with FH was higher in men than in women in all age groups presented, with no differences between the FH sample and the non-FH controls. However, the relative risk in FH compared with controls was similar for both sexes.
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- 2020
8. Postprandial changes in gene expression of cholesterol influx and efflux mediators after intake of SFA compared with
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Linn K L, Øyri, Ingunn, Narverud, Martin P, Bogsrud, Patrik, Hansson, Lena, Leder, Marte G, Byfuglien, Marit B, Veierød, Magne, Thoresen, Stine M, Ulven, and Kirsten B, Holven
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Adult ,Male ,Fat quality ,Fatty Acids ,LDLR, LDL receptor ,food and beverages ,Gene Expression ,LDL receptor ,LDL-C, LDL-cholesterol ,SREBP, sterol regulatory element binding protein ,Postprandial Period ,Hyperlipoproteinemia Type II ,Young Adult ,Cholesterol ,Receptors, LDL ,PBMC, peripheral blood mononuclear cells ,Homeostasis ,Humans ,lipids (amino acids, peptides, and proteins) ,Female ,Postprandial responses ,CT, cycle threshold ,Familial hypercholesterolaemia ,Research Article ,FH, familial hypercholesterolaemia - Abstract
The long-term cholesterol-lowering effect of replacing intake of SFA with PUFA is well established, but has not been fully explained mechanistically. We examined the postprandial response of meals with different fat quality on expression of lipid genes in peripheral blood mononuclear cells (PBMC) in subjects with and without familial hypercholesterolaemia (FH). Thirteen subjects with FH (who had discontinued lipid-lowering treatment ≥4 weeks prior to both test days) and fourteen normolipidaemic controls were included in a randomised controlled double-blind crossover study with two meals, each with 60 g of fat either mainly SFA (about 40% energy) or n-6 PUFA (about 40% energy). PBMC were isolated in fasting, and 4 and 6 h postprandial blood samples. Expression of thirty-three lipid genes was analysed by reverse transcription quantitative PCR. A linear mixed model was used to assess postprandial effects between meals and groups. There was a significant interaction between meal and group for MSR1 (P = 0·03), where intake of SFA compared with n-6 PUFA induced a larger reduction in gene expression in controls only (P = 0·01). Intake of SFA compared with n-6 PUFA induced larger reductions in gene expression levels of LDLR and FADS1/2, smaller increases of INSIG1 and FASN, and larger increases of ABCA1 and ABCG1 (P = 0·01 for all, no group interaction). Intake of SFA compared with n-6 PUFA induced changes in gene expression of cholesterol influx and efflux mediators in PBMC including lower LDLR and higher ABCA1/G1, potentially explaining the long-term cholesterol-raising effect of a high SFA intake.
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- 2019
9. Hyperlipidemia and cardiovascular disease with focus on familial hypercholesterolemia
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Stine Marie Ulven, Martin P. Bogsrud, and Kirsten B. Holven
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Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Familial hypercholesterolemia ,Disease ,030204 cardiovascular system & hematology ,Hyperlipoproteinemia Type II ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Hyperlipidemia ,Genetics ,Medicine ,Humans ,030212 general & internal medicine ,Cholesterol metabolism ,Molecular Biology ,Focus (computing) ,Nutrition and Dietetics ,business.industry ,Cholesterol ,Cell Biology ,Middle Aged ,medicine.disease ,chemistry ,Cardiovascular Diseases ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Published
- 2017
10. Lipidprofil ved lavkarbokosthold hos friske
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Kjetil Retterstøl, Martine Zakariassen Espeland, Ane Sørlie Kværner, Monica Baumann, and Martin P. Bogsrud
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Ldl cholesterol ,medicine.medical_specialty ,medicine.diagnostic_test ,Cholesterol ,business.industry ,Saturated fat ,Weight change ,General Medicine ,Carbohydrate ,Individual risk ,chemistry.chemical_compound ,Endocrinology ,Animal science ,chemistry ,Internal medicine ,medicine ,Lipid profile ,business ,Low carbohydrate - Abstract
BACKGROUND: Many Norwegians have embraced the low-carb trend and choose butter and bacon instead of brown bread and carrots. This entails a dramatic change in the total intake of fat and the intake of saturated fat. We have investigated how a low-carb diet can affect the lipid profile in healthy adults with a normal bodyweight. MATERIAL AND METHOD: Seven healthy female participants with normal bodyweight underwent a four-week trial of a low-carb diet (< 20-25 grams of carbohydrates/day). Daily diet registrations were made during the trial period, and diet data for three randomly selected days were included in the estimates. Blood samples and weight data were collected as fasting values prior to and after the intervention. RESULTS: Standardised diet data were available for six participants. On a low-carb diet, the energy intake from carbohydrates accounted for a median of 3 (spread: 2-5) per cent of the total energy intake. The intake of fat accounted for 71 (67-78) per cent of total energy, while protein accounted for 26 (19-31) of total energy intake. At baseline, the median value of total cholesterol was 4.1 mmol/L (dispersion: 3.3-5.7) and LDL cholesterol was 2.2 (1.8-3.4) mmol/L. The values increased to 5.2 (3.7-8.8) mmol/L and 3.1 (1.9-6.2) mmol/L for total and LDL cholesterol respectively. The absolute changes correspond to a percentage increase in total cholesterol of 33 (14-71)% and in LDL cholesterol of 41 (9-84)%. Median weight change amounted to -1.2 kg (-2.8-0.6). INTERPRETATION: A diet with little carbohydrate and a great deal of protein and fat resulted in a considerably heightened level of total cholesterol and LDL cholesterol in young, healthy women with a normal bodyweight. The findings indicate that a low-carb diet may have a negative impact on individual risk profiles. However, the study is small-scale and the results must be interpreted with caution.
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- 2013
11. 3.2% OF YOUNG SUBJECTS UNDER 45 YEARS WITH ACUTE MYOCARDIAL INFARCTION HAVE GENETICALLY VERIFIED FAMILIAL HYPERCHOLESTEROLEMIA
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Trond P. Leren, Dan Atar, Martin P. Bogsrud, Linn Kristin Lie Øyri, Kirsten B. Holven, and Sigrun Halvorsen
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medicine.medical_specialty ,business.industry ,First myocardial infarction ,Mean age ,Early death ,Norwegian ,Disease ,Familial hypercholesterolemia ,medicine.disease ,language.human_language ,Increased risk ,Internal medicine ,language ,medicine ,Cardiology ,lipids (amino acids, peptides, and proteins) ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business - Abstract
Patients with familial hypercholesterolemia (FH) have increased total- and LDL-cholesterol levels and thus an increased risk of premature cardiovascular disease (CVD) and early death. Mean age of first myocardial infarction (MI) in Norwegian FH patients was recently shown to be 44 years. The aim of
- Published
- 2018
12. Familial hypercholesterolaemia: A global call to arms
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Carolyn S.P. Lam, Evangelos Liberopoulos, Pedro Mata, Ta-Chen Su, John O'Donoghue, Elisabeth Widen, Amirhossein Sahebkar, Gustavs Latkovskis, Khalid Al-Rasadi, Olivier S. Descamps, John J.P. Kastelein, Gerald F. Watts, Tomáš Freiberger, I.M. Gaspar, Hans Dieplinger, Mariko Harada-Shiba, Handrean Soran, Rodrigo Alonso, Alberico L. Catapano, Della Cole, Meral Kayıkçıoğlu, Marianne Abifadel, Maciej Banach, J. Genest, Heribert Schunkert, Pablo Corral, Ronen Durst, Sreenivasa Rao Kondapally Seshasai, Martin P. Bogsrud, Antonio J. Vallejo-Vaz, Lixin Jiang, Frederick J. Raal, Josip Car, Børge G. Nordestgaard, Kausik K. Ray, Lennart Nilsson, Andrey V. Susekov, Ulrich Laufs, Raul D. Santos, Asif Akram, Mario Stoll, Mafalda Bourbon, Eric Bruckert, G. Kees Hovingh, Carlos A. Aguilar-Salinas, Abdulla Shehab, Fahad Alnouri, Pfizer Incorporated, ACS - Amsterdam Cardiovascular Sciences, and Vascular Medicine
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Pathology ,Apolipoprotein B ,Disease ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Global Health ,DISEASE ,Doenças Cardio e Cérebro-vasculares ,0302 clinical medicine ,Hyperlipoproteinemia Type II ,Societies, Medical ,RISK ,0303 health sciences ,Mutation ,biology ,3. Good health ,PREVALENCE ,Europe ,lipids (amino acids, peptides, and proteins) ,Cardiology and Cardiovascular Medicine ,Familial hypercholesterolaemia ,Life Sciences & Biomedicine ,medicine.medical_specialty ,Heterozygote ,1102 Cardiovascular Medicine And Haematology ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,030304 developmental biology ,Science & Technology ,business.industry ,GUIDANCE ,PCSK9 ,Heterozygote advantage ,1103 Clinical Sciences ,Endocrinology ,Peripheral Vascular Disease ,Cardiovascular System & Hematology ,Receptors, LDL ,RECEPTORES DE LIPOPROTEÍNAS ,Relative risk ,biology.protein ,Cardiovascular System & Cardiology ,Familial Hypercholesterolaemia ,business ,CLINICIAN ,Lipoprotein - Abstract
Familial Hypercholesterolaemia (FH) is the commonest autosomal co-dominantly inherited condition affecting man. It is caused by mutation in one of three genes, encoding the low-density lipoprotein (LDL) receptor, or the gene for apolipoprotein B (which is the major protein component of the LDL particle), or in the gene coding for PCSK9 (which is involved in the degradation of the LDL-receptor during its cellular recycling). These mutations result in impaired LDL metabolism, leading to life-long elevations in LDL-cholesterol (LDL-C) and development of premature atherosclerotic cardiovascular disease (ASCVD) [1], [2] and [3]. If left untreated, the relative risk of premature coronary artery disease is significantly higher in heterozygous patients than unaffected individuals, with most untreated homozygotes developing ASCVD before the age of 20 and generally not surviving past 30 years [2], [3], [4] and [5]. Although early detection and treatment with statins and other LDL-C lowering therapies can improve survival, FH remains widely underdiagnosed and undertreated [1], thereby representing a major global public health challenge.
- Published
- 2015
13. Kostholdsråd ved høye blodlipider
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Linn Øyri, Dan Johansen, Kirsten B. Holven, Martin P. Bogsrud, Asta Ellingvåg, and Ellen C. Strøm
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- 2016
14. Altered leukocyte distribution under hypercholesterolemia: A cross-sectional study in children with familial hypercholesterolemia
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Jacob J. Christensen, Liv Osnes, Bente Halvorsen, Kjetil Retterstøl, Martin P. Bogsrud, Cecilie Wium, Arne Svilaas, Ingunn Narverud, Stine M. Ulven, Pål Aukrust, and Kirsten B. Holven
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2017
15. Postprandial response after intake of saturated fat compared to polyunsaturated fat in subjects with familial hypercholesterolemia and normolipidemic controls-a randomized controlled trial
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Ingunn Narverud, Linn Kristin Lie Øyri, Marit B. Veierød, Lena Leder, Stine Marie Ulven, Magne Thoresen, Kirsten B. Holven, Martin P. Bogsrud, Patrik Hansson, Geir Florholmen, and Marte Gjeitung Byfuglien
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medicine.medical_specialty ,business.industry ,Saturated fat ,Familial hypercholesterolemia ,medicine.disease ,law.invention ,Polyunsaturated fat ,Postprandial ,Endocrinology ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Cardiology and Cardiovascular Medicine ,business - Published
- 2017
16. UGT1A1*28 is associated with decreased systemic exposure of atorvastatin lactone
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Monica Hermann, Kjetil Retterstøl, Armin P. Piehler, Camilla Stormo, Marianne K. Kringen, Martin P. Bogsrud, and Anders Åsberg
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Adult ,Male ,Glucuronosyltransferase ,Genotype ,Metabolite ,Atorvastatin ,Glucuronidation ,Pharmacology ,chemistry.chemical_compound ,Lactones ,Pharmacokinetics ,Muscular Diseases ,Genetics ,Medicine ,Humans ,Pyrroles ,Alleles ,Whole blood ,chemistry.chemical_classification ,Polymorphism, Genetic ,biology ,business.industry ,Cholesterol ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,chemistry ,Heptanoic Acids ,biology.protein ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Female ,business ,Lactone ,medicine.drug - Abstract
Atorvastatin is commonly used to reduce cholesterol. Atorvastatin acid is converted to its corresponding lactone form spontaneously or via glucuronidation mediated by uridine diphosphate glucuronosyltransferase (UGT) 1A1 and 1A3. Atorvastatin lactone is pharmacologically inactive, but is suspected to be muscle toxic and cause statin-induced myopathy (SIM). A several fold increase in systemic exposure of atorvastatin lactone has previously been observed in patients with SIM compared with healthy control subjects. In this study we aimed to investigate the association between polymorphisms in the UGT1A gene locus and plasma atorvastatin lactone levels. DNA was extracted from whole blood obtained from a previous pharmacokinetic study of patients carefully diagnosed as having true SIM (n = 13) and healthy control subjects (n = 15). The UGT1A1*28(TA) 7 , UGT1A3*2, UGT1A3*3, and UGT1A3*6 polymorphisms were detected by pyrosequencing. Carriers of the low-expression allele UGT1A1*28(TA) 7 tended to have lower levels of atorvastatin lactone (p
- Published
- 2013
17. Exposure of atorvastatin is unchanged but lactone and acid metabolites are increased several-fold in patients with atorvastatin-induced myopathy
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Martin P. Bogsrud, Beata U. Mohebi, Espen Molden, Monica Hermann, Anders Åsberg, Kjetil Retterstøl, and Leiv Ose
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Adult ,Male ,Organic anion transporter 1 ,Side effect ,Genotype ,Metabolite ,Atorvastatin ,Organic Anion Transporters ,Pharmacology ,chemistry.chemical_compound ,Lactones ,Pharmacokinetics ,Cytochrome P-450 Enzyme System ,Muscular Diseases ,medicine ,Cytochrome P-450 CYP3A ,Humans ,Pharmacology (medical) ,Pyrroles ,cardiovascular diseases ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Myopathy ,Creatine Kinase ,Aged ,biology ,Liver-Specific Organic Anion Transporter 1 ,Anticholesteremic Agents ,nutritional and metabolic diseases ,Middle Aged ,chemistry ,Liver ,Heptanoic Acids ,Case-Control Studies ,Creatinine ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Creatine kinase ,Female ,medicine.symptom ,SLCO1B1 ,medicine.drug - Abstract
Background The most serious side effect from statin treatment is myopathy, which may proceed to rhabdomyolysis. This is the first study to investigate whether the pharmacokinetics of either atorvastatin or its metabolites, or both, is altered in patients with atorvastatin-related myopathy compared with healthy controls. Methods A 24-hour pharmacokinetic investigation was performed in 14 patients with atorvastatin-related myopathy. Relevant polymorphisms in SLCO1B1 (encoding organic anion transporting polypeptide 1B1), MDR1/ABCB1 (encoding P-glycoprotein), and CYP3A5 (encoding cytochrome P450 3A5) were determined. Data from 15 healthy volunteers were used as controls. Results No statistically significant difference in systemic exposure of atorvastatin was observed between the 2 groups. However, patients with atorvastatin-related myopathy had 2.4-fold and 3.1-fold higher systemic exposures of the metabolites atorvastatin lactone (P < .01) and p-hydroxyatorvastatin (P < .01), respectively, compared with controls. There were no differences in frequencies of SLCO1B1, MDR1, and CYP3A5 polymorphisms between the 2 groups. Conclusions This study disclosed a distinct difference in the pharmacokinetics of atorvastatin metabolites between patients with atorvastatin-related myopathy and healthy control subjects. These results are of importance in the further search for the mechanism of statin-induced myopathy. Clinical Pharmacology & Therapeutics (2006) 79, 532–539; doi: 10.1016/j.clpt.2006.02.014
- Published
- 2005
18. M. Baumann og medarbeidere svarer
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Monica Baumann, Ane Sørlie Kværner, Martine Zakariassen Espeland, Martin P. Bogsrud, and Kjetil Retterstøl
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business.industry ,Medicine ,General Medicine ,business - Published
- 2013
19. 69 HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA IN NORWAY, SWEDEN, DENMARK AND FINLAND – SUBSTANTIAL VARIATION IN FREQUENCY OF THE DIAGNOSIS
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Kjetil Retterstøl, A. Græsdal, G. Langslet, Martin P. Bogsrud, Leiv Ose, and Y. Stålstrøm
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Variation (linguistics) ,business.industry ,Internal Medicine ,Medicine ,General Medicine ,Familial hypercholesterolemia ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Demography - Published
- 2011
20. Abstract: 102 THE EFFECT OF Q10 AND SELENIUM SUPPLEMENT ON ADVERSE EFFECTS IN STATIN TREATMENT
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Kjetil Retterstøl, B Woldseth, Martin P. Bogsrud, Leiv Ose, and U Malt
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chemistry ,business.industry ,Internal Medicine ,chemistry.chemical_element ,Medicine ,General Medicine ,Statin treatment ,Pharmacology ,Cardiology and Cardiovascular Medicine ,Adverse effect ,business ,Selenium - Published
- 2009
21. Th-P16:266 The effect of red yeast rice on lipids, inflammatory markers and glucose in subjects with mild hypercholesterolemia and mildly elevated blood glucose
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Kjetil Retterstøl, G. Langslet, Martin P. Bogsrud, Leiv Ose, and I. Ottestad
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medicine.medical_specialty ,Endocrinology ,Elevated blood glucose ,business.industry ,Internal medicine ,Internal Medicine ,medicine ,Red yeast rice ,General Medicine ,Cardiology and Cardiovascular Medicine ,business - Published
- 2006
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