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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.
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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.
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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. This study was registered at clinicaltrials.gov as NCT03580057.
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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.
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Doença das Coronárias , Perfilação da Expressão Gênica , Hiperlipoproteinemia Tipo II , Humanos , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/sangue , Masculino , Feminino , Idoso , Doença das Coronárias/genética , Estudos de Casos e Controles , Leucócitos Mononucleares/metabolismo , Fatores Etários , Transcriptoma , Idoso de 80 Anos ou maisRESUMO
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.
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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.
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Idoso Fragilizado , Fragilidade , Idoso , Masculino , Humanos , Feminino , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Estudos Transversais , Fator de Crescimento Insulin-Like I , Cistatina C , Interleucina-6 , Leucócitos Mononucleares , Inflamação/diagnóstico , Inflamação/epidemiologia , Catepsinas , Avaliação Geriátrica/métodosRESUMO
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.
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Aterosclerose , Doenças Cardiovasculares , Cisteína Endopeptidases , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Criança , Adulto Jovem , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fatores de Risco , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/genética , Fatores de Risco de Doenças CardíacasRESUMO
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.
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Aterosclerose , Doenças Cardiovasculares , Animais , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/complicações , Gorduras na Dieta , Lipoproteínas , Lipoproteínas LDL , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
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. Clinical Trial Registration: Clinicaltrials.gov, identifier (NCT05030922).
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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. 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.
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Aterosclerose , Hiperlipoproteinemia Tipo II , Feminino , Humanos , Masculino , Criança , Adulto , LDL-Colesterol , Caracteres Sexuais , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Aterosclerose/epidemiologia , Aterosclerose/etiologiaRESUMO
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. 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 .
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Ganho de Peso na Gestação , Gravidez , Feminino , Humanos , Lactação , Obesidade/terapia , Aumento de Peso , Dieta , Período Pós-Parto , Redução de Peso , Glucose , LipídeosRESUMO
Differences between men and women in lipids and lipoproteins are observed in distribution and trajectory from infancy to adulthood in the general population. However, these differences are more pronounced in hereditary lipid disorders such as familial hypercholesterolemia (FH) when absolute cholesterol levels are higher from birth onwards. In the early life course, girls compared to boys have higher low-density lipoprotein cholesterol (LDL-C) levels and total cholesterol, while high-density lipoprotein cholesterol (HDL-C) levels are similar. In early adulthood to middle-age, women have lower LDL-C and higher HDL-C levels, as LDL-C levels increase and HDLC levels decrease in men. In the elderly, all lipids - total cholesterol, LDL-C, HDL-C and triglyceride levels decrease but are more pronounced in men. Lipid levels are also affected by specific transitions in girls/women such as the menstrual cycle, pregnancy, breastfeeding and menopause. Lipid levels fluctuate during the menstrual cycle. During pregnancy a physiological increase of LDL-C and even a larger increase in triglyceride levels are observed. Pregnancy has a double impact on LDL-C accumulation in women with FH as they have to stop statins, and the absolute increase in LDL-C is higher than in women without FH. In the menopausal transition, women develop a more adverse lipid profile. Therefore, it is important to take into account both sex and the life course when assessing a lipid profile.
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Colesterol , Hiperlipoproteinemia Tipo II , Pessoa de Meia-Idade , Gravidez , Humanos , Masculino , Feminino , Idoso , LDL-Colesterol , Caracteres Sexuais , Acontecimentos que Mudam a Vida , HDL-Colesterol , TriglicerídeosRESUMO
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.
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Aterosclerose , Doenças Cardiovasculares , Masculino , Pessoa de Meia-Idade , Gravidez , Humanos , Feminino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/complicações , Aterosclerose/etiologia , Lipoproteína(a) , Fatores de RiscoAssuntos
Colesterol , Lipoproteínas , Lactente , Humanos , Lipoproteínas/sangue , Colesterol/sangue , ApolipoproteínasRESUMO
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.
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Doenças Cardiovasculares , Ácidos Graxos Ômega-3 , Humanos , Triglicerídeos , Ácido Eicosapentaenoico/metabolismo , Ácidos Docosa-Hexaenoicos , Doenças Cardiovasculares/prevenção & controle , Suplementos NutricionaisRESUMO
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 (ß = - 0.090, 95% CI = (- 0.146, - 0.034), p-value = 0.002 for gait speed, and ß = - 0.206, 95% CI = (- 0.385, - 0.028), p-value = 0.024 for ASMI), and gait speed associated with CIBERSORT-estimated M2 macrophage proportions (ß = - 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 (ß in the range - 0.007 to 0.008, p-values < 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.
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Força da Mão , Leucócitos Mononucleares , Humanos , Feminino , Idoso , Força da Mão/fisiologia , Transcriptoma , Estudos Transversais , Força Muscular , Músculo Esquelético , Desempenho Físico FuncionalRESUMO
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.
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Dieta Mediterrânea , Hiperlipoproteinemia Tipo II , Humanos , Estudos Transversais , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Lipoproteínas/genética , Fenótipo , Gorduras na DietaRESUMO
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.
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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.