Search

Heart failure with preserved ejection fraction (HFpEF) is a disorder related to patient comorbidities and aging. Whether mitochondrial dysfunction is present during HFpEF decompensation versus the stable phase is largely unknown. The aim of the present study was to identify mitochondrial and cell metabolism blood biomarkers in older patients with acute and stable HFpEF.Peripheral blood biomarkers were investigated in a group of eight to 12 patients aged 80-96 years and diagnosed with HFpEF first when they were in decompensated phase and then at least three months later in stable phase. Their data were compared to two control groups with an equal number of participants and sex proportions. One group was age matched and the other included individuals aged between 22 and 44 years.Decompensated patients experienced an increased mitochondrial superoxide production and mitochondrial mass, lower mitochondrial DNA copy number and LDHB expression, and higher lactate level compared to the stable stage. The stable phase was characterized by a sharp reduction in formate level. Multivariate analysis indicated that formate, lactate, and histidine can distinguish both of the HFpEF phases. Many of these parameters, including LDHB, lactate, formate, and mitochondrial mass, followed an age-related pattern, with acute HFpEF at its apex or nadir, suggesting that it represents an exacerbation of an aging-related process.We identified distinct blood biomarkers of chronic and decompensated HFpEF phases. The data underlined the relationship between HFpEF and aging. These findings could be used to monitor patients and might be therapeutically targeted.

Resumen Introduccion y objetivos Varios tipos de lipoproteinas, aparte de las lipoproteinas de baja densidad (LDL), tienen relacion causal con la enfermedad cardiovascular. Se analizo el perfil lipoproteico avanzado de individuos con metabolismo glucemico normal y alterado provenientes de una region mediterranea. Metodos Estudio transversal en 929 participantes (463 normoglucemicos, 250 prediabeticos y 216 con diabetes tipo 2) sin insuficiencia renal, enfermedad cardiovascular ni tratamiento hipolipemiante. Se analizaron los perfiles lipoproteicos convencional y avanzado (resonancia magnetica [RM] espectroscopica). Resultados En comparacion con los varones, las mujeres normoglucemicas mostraron menores concentraciones de trigliceridos y cLDL, menos particulas (P) de LDL y todas sus subclases y menos contenido en colesterol y trigliceridos, mayor concentracion de P de lipoproteinas de alta densidad (HDL) y de todas sus variables relacionadas (p ≤ 0,05 para todas las comparaciones). En comparacion con los normoglucemicos, los diabeticos mostraron una mayor concentracion de P-VLDL grandes y pequenas (p Conclusiones Las mujeres mostraron un mejor perfil lipoproteico avanzado que los varones. Se hallo relacion directa de los indices de adiposidad relacionados con resistencia insulinica con un perfil lipidico proaterogenico. La RM mostro alteraciones en particulas lipoproteicas distintas de las LDL en los diabeticos, a menudo asociadas con mayor riesgo cardiovascular. Nuestros hallazgos confirman la utilidad del analisis lipoproteico avanzado mediante RM espectroscopica para descubrir nuevas dianas terapeuticas con que prevenir eventos cardiovasculares en los individuos en riesgo.

Bicuspid aortic valve; Glycoprotein; Lipoprotein metabolism Vàlvula aòrtica bicúspide; Glicoproteïna; Metabolisme de les lipoproteïnes Válvula aórtica bicúspide; Glicoproteína; Metabolismo de las lipoproteínas Introduction: The bicuspid aortic valve (BAV) confers a high risk of ascending aorta dilatation (AAoD), although its progression seems highly variable. Furthermore, the implication of lipoprotein metabolism and inflammation in the mechanisms that underlie AAoD is not fully established. The aim of this study consisted of evaluating the impact of the lipoprotein and glycoprotein profiles in AAOD as well as its progression in BAV aortopathy. Methods: Using 1H-nuclear magnetic resonance (1H-NMR), we analyzed and compared the lipoprotein and glycoprotein profiles of plasma samples from 152 BAV patients with dilated and nondilated ascending aorta. Additionally, these profiles were also compared for 119 of these patients who were prospectively followed-up clinically and by echocardiography in the long-term (5 years). Ascending aorta dilation velocity (mm/year) was calculated for this analysis. Results: Several parameters related to the lipoprotein profile including remnant cholesterol, small LDL and IDL-cholesterol were found to be significantly increased in the dilated group compared to those in the nondilated group. The glycoprotein A-nuclear magnetic resonance (NMR) signal, a novel inflammation biomarker, was also observed to be increased in the dilated group. After performing multivariate analysis, remnant cholesterol remained an independent variable related to AAoD. In the long-term follow-up, proatherogenic lipoprotein parameters were related to ascending aorta dilatation velocity ascending. After a lineal regression analysis, non-HDL particles remained as an independent predictor of ascending aorta dilation velocity. Conclusions: Patients with BAV and AAoD presented a more pro-atherogenic profile assessed by 1H-NMR, especially related to triglyceride-rich lipoproteins. This pro-atherogenic profile seems to contribute to the higher growth rate of ascending aorta diameter. This research was funded by “Proyectos de Investigación Clínica” from the Spanish Society of Cardiology, grant Bayer 2019. BA-G received a research scholarship within the Martí-Franquès Research Fellowship Program from the University of Rovira i Virgili.

This study evaluated the preclinical effect of obesity on the ventricular remodeling in adolescents with morbid obesity, and determined if subjects labelled as metabolically healthy obesity (MHO) presented better heart index than those with metabolically unhealthy obesity (MUO). Prospective case-control research of 45 adolescents (14-year-old) with morbid obesity and 25 normal weight adolescents' gender- and age-matched with Tanner stage 4-5. Left ventricle (LV) was evaluated by conventional Doppler echocardiography, tissue Doppler imaging and two-dimensional speckle tracking echocardiography. Compared to normal-weight subjects, adolescents with morbid obesity presented a high percentage of pathological LV geometry (87%; p

Background and aims Inflammation is a pathophysiological mechanism of atherosclerosis, and several mediators have been proposed as biomarkers. Acute-phase serum glycoproteins are upregulated in the liver during systemic inflammation. Because of their unique biochemical characteristics, they can be measured by 1H-NMR, and their role as subclinical inflammation markers is under clinical evaluation. We aimed to assess the clinical value of plasma glycoproteins in familial hypercholesterolemia (FH) patients. Methods We recruited 295 FH patients (75.6% with FH-associated genetic variants). At baseline, a full glycoprotein profile, glycoprotein A and B (GlycA and B) concentrations and their height and width ratios (H/W) were analysed by 1H-NMR. A carotid artery ultrasound study was performed at baseline and prospectively at the 5-year follow-up in 144 FH patients. Results At baseline, the GlycA and GlycB concentrations and their H/W ratios were correlated with lipid profile and adiposity parameters, with the correlation between the GlycA and triglyceride concentrations (r = 0.780; p Conclusions The concentrations of serum glycoproteins as assessed by 1H-NMR are robust markers of subclinical inflammation. In FH patients, they are increased in the presence of subclinical vascular damage and could be considered atherosclerosis risk markers in the long term.

OBJECTIVE Vascular aging (arterial stiffness [AS]) is an inflammation-linked process that predicts macro- and microvascular complications in adults with type 1 diabetes (T1D). We evaluated the utility of measuring the inflammation-linked N-glycans GlycA and GlycB to assess vascular aging in adults with T1D. RESEARCH DESIGN AND METHODS Eighty-four adults with T1D (>10-year duration without cardiovascular events) and 68 healthy control subjects were evaluated for clinical characteristics (including microvascular complications in patients with T1D), aortic pulse wave velocity (aPWV) (surrogate measure of AS), and serum GlycA and GlycB (peak area [concentration] and height/width [H/W] ratio) using 1H-nuclear magnetic resonance spectroscopy. RESULTS Patients with T1D had higher median (interquartile range) values than healthy control subjects for (P < 0.001 for all comparisons) aPWV 7.9 (6.9–9.1) vs. 6.1 (5.5–6.7) m/s, GlycA 850.4 (781.3–916.1) vs. 652.4 (581.5–727.1) μmoL; GlycB 386.1 (353.2–426.3) vs. 310.0 (280.5–331.9) μmol/L), H/W ratio of GlycA 16.5 (14.9–18.1) vs. 15.0 (13.7–16.7), and H/W ratio of GlycB 5.0 (4.6–5.5) vs. 4.0 (3.4–4.3). Moreover, aPWV correlated (P < 0.001 for all correlations) with GlycA (r = 0.550) and GlycB (r = 0.423) concentrations and with H/W ratios of GlycA (r = 0.453) and GlycB (r = 0.510). Adjusting for potential confounders, GlycA concentration (β = 0.212, P < 0.001) and the H/W ratios of GlycA (β = 0.150, P = 0.009) and GlycB (β = 0.155, P = 0.011) remained independently associated with aPWV. C-statistics for detecting individuals with aPWV >10 m/s were 0.866 (95% CI 0.794–0.937) for GlycA levels and 0.862 (0.780–0.943) for H/W ratio of GlycB. CONCLUSIONS Measurement of serum GlycA and GlycB may have utility in assessing vascular aging in adults with T1D of >10-year duration and no previous cardiovascular events.

Objectivechronic inflammation and immune dysregulation are crucial mechanisms for atherosclerosis in rheumatoid arthritis (RA). Recent evidence suggests a link via humoral responses against high-density lipoproteins (HDL). However, their specificity, clinical relevance and emergence along disease course are unknown, especially during the earliest phases of RA.MethodsIgG and IgM serum levels of antibodies against HDL (anti-HDL) and Apolipoprotein A1 (anti-ApoA1) were measured in 82 early RA patients, 14 arthralgia individuals and 96 controls. Established RA patients (n=42) were included for validation. Atherosclerosis and vascular stiffness were measured by Doppler-ultrasound. Lipoprotein content, particle numbers and size were measured by H-NMR. Cytokines were measured by immunoassays. A cardiometabolic-related protein panel was evaluated using high- throughput targeted proteomics.Resultsanti-HDL and anti-ApoA1 responses were increased in early RA compared to controls (both pConclusionhumoral responses against HDL particles are an early event along arthritis course, although quantitative and qualitative differences can be noticed among stages. These differences informed distinct capacities as biomarkers and underlying pathogenic circuits.

Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors (age, sex, genetic factors, lipid disorders, heart failure, gut dysbiosis, diet, vitamin D deficiency, air pollution and exposure to chemicals) influence COVID-19 by applying the Adverse Outcome Pathway (AOP), which is well-established in regulatory toxicology. This framework aims to model the sequence of events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how those eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.

Resumen La evaluacion y prevencion del riesgo cardiovascular (RCV) que persiste en los pacientes con dislipidemia a pesar del tratamiento y de haber alcanzado los objetivos especificos de la concentracion plasmatica de colesterol unido a lipoproteinas de baja densidad (c-LDL) es un reto clinico en la actualidad, y sugiere que los biomarcadores lipidicos convencionales resultan insuficientes para una evaluacion precisa del RCV. Mas alla de su contenido lipidico, existen otras caracteristicas propias de las particulas lipoproteicas que determinan su potencial aterogenico y su influencia en el RCV. Sin embargo, dichas caracteristicas adicionales no pueden ser analizadas por las tecnicas utilizadas habitualmente en los laboratorios clinicos. La espectroscopia por resonancia magnetica nuclear (RMN) es una tecnica que permite un analisis detallado de la cantidad, composicion y tamano de las lipoproteinas y proporciona informacion mas detallada del estado del metabolismo lipidico y del RCV en los pacientes dislipemicos. En este articulo un grupo de lipidologos de la Sociedad Espanola de Arteriosclerosis revisa la evidencia existente sobre los mecanismos aterogenicos de las particulas lipoproteicas y describen el fundamento tecnico y la interpretacion de los perfiles lipoproteicos obtenidos mediante RMN, haciendo especial referencia al test disponible en Espana (Liposcale®). Asimismo, se definen los principales perfiles de pacientes en los que dicho analisis aportaria una informacion de mayor interes clinico, los cuales son: a) sospecha de discordancia entre las concentraciones de lipidos y el numero de particulas, situacion frecuente en la diabetes, la obesidad, el sindrome metabolico y la hipertrigliceridemia; b) enfermedad cardiovascular aterotrombotica (ECVA) precoz o recurrente sin factores de RCV que la justifiquen; c) trastornos lipidicos infrecuentes o complejos como las concentraciones extremas de c-HDL, y d) situaciones clinicas en las que las tecnicas analiticas clasicas no pueden aplicarse, como los valores de c-LDL muy bajos.

The assessment and prevention of cardiovascular risk (CVR) that persists in patients with dyslipidaemia despite treatment and achievement of goals specific to the plasma concentration of cholesterol linked to low density (c-LDL) is a clinical challenge today, and suggests that conventional lipid biomarkers are insufficient for an accurate assessment of CVR. Apart from their lipid content, there are other lipid particle characteristics. The results of this study show that there are a number of lipoprotein compounds that determine atherogenic potential and its influence on the CVR. However, such additional characteristics cannot be analysed by the techniques commonly used in clinical laboratories. Nuclear Magnetic Resonance (NMR) is a technique that allows a detailed analysis to be made of the amount, composition, and size of lipoproteins, as well as providing more information about the detailed status of lipid metabolism and CVR in dyslipidaemia patients. In this article a group of lipidologists from the Spanish Society of Arteriosclerosis review the existing evidence on the atherogenic mechanisms of particles and describe the technical basis and interpretation of the profiles lipoproteins obtained by MRI, with special reference to the test available in Spain (Liposcale®). Likewise, the main patient profiles are defined as such that an analysis would provide information of greater clinical interest. These include: a) Suspected mismatch between lipid concentrations and particles, a common situation in diabetes, obesity, metabolic syndrome; b) Early atherothrombotic cardiovascular disease (ECVA) or recurrent without CVR factors to justify it; c) Lipid disorders, rare or complex, such as extreme concentrations of c-HDL, and d) Clinical situations where classical analytical techniques cannot be applied, such as very low c-LDL values.

Preeclampsia (PE) and fetal growth restriction (FGR) are both placenta-mediated disorders with unclear pathogenesis. Metabolomics of maternal and fetal pairs might help in understanding these disorders. We recruited prospectively pregnancies with normotensive FGR, PE without FGR, PE + FGR and uncomplicated pregnancies as controls. Nuclear magnetic resonance metabolomics were applied on plasma samples collected at delivery. Advanced lipoprotein, glycoprotein and choline profiling was performed using the Liposcale test. The software package Dolphin was used to quantify 24 low-molecular-weight metabolites. Statistical analysis comprised the comparison between each group of complicated pregnancies versus controls, considering 5% false discovery rate correction. Lipid profiles were altered in accordance with the clinical presentation of these disorders. Specifically, PE mothers and FGR fetuses (with or without FGR or PE, respectively) exhibited a pro-atherogenic and pro-inflammatory profile, with higher concentrations of triglycerides, remnant cholesterol (VLDL, IDL) and Glc/GalNAc-linked and lipid-associated glycoproteins compared to controls. Low-molecular-weight metabolites were extensively disturbed in preeclamptic mothers, with or without FGR. Growth restricted fetuses in the presence of PE showed changes in low-molecular-weight metabolites similar to their mothers (increased creatine and creatinine), while normotensive FGR fetuses presented scarce differences, consistent with undernutrition (lower isoleucine). Further research is warranted to clarify maternal and fetal adaptations to PE and FGR.

Altres ajuts: Fundació La Marató de TV3 (303/C/2016)(201602.30.31) Aims: The impact of glycemic optimization on lipoprotein subfraction parameters in apparently normolipidemic subjects with new-onset type 1 diabetes mellitus (T1D) was examined. Methods: We evaluated the serum lipid and advanced lipoprotein profiles in twenty subjects at onset of T1D and twenty non-diabetic controls by laboratory methods and 1H NMR spectroscopy shortly after diabetes diagnosis (baseline), and after achieving optimal glycemic control (HbA1c ≤ 7.0%). Results: Advanced lipoprotein analysis revealed a significant reduction from baseline in serum concentrations of triglycerides (TG), cholesterol (C), and apolipoprotein (Apo)B-containing lipoproteins of treated subjects (VLDL-TG: −21%, IDL-TG: −30%, LDL-TG: −34%, LDL-TG: −36%, P < 0.05; VLDL-C: -23%, IDL-C: −44%, LDL-C: −16%; p < 0.05). Decreased VLDL and LDL lipids were mainly attributed to concomitant reductions in the concentration of medium-sized VLDL (-36%) and medium-sized LDL (-31%) and, to a lesser extent, to large-sized LDL (-14%). Notably, proatherogenic IDL characteristics and related surrogates of atherogenicity were resolved upon achievement of optimal glycemic status. Moreover, the concentration of HDL-TG was also reduced (−18%) at follow-up. Conclusions: Our data showed that the achievement of optimal glycemic control after T1D onset corrected hidden derangements in ApoB-containing lipoproteins (particularly IDL) and HDL-TG that are related to higher cardiovascular risk in poorly controlled T1D.

The polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women in reproductive age. Obesity and low-grade chronic inflammation are frequently associated with PCOS. Recently, proton nuclear magnetic resonance (1H-NMR)-derived glycoprotein profiles have emerged as potential biomarkers that reflect systemic inflammation in type 2 diabetes, obesity, and other pathological processes. The aim of this work is to study plasma glycoprotein profiles as metabolic/inflammatory biomarkers underlying PCOS and its association with inflammation and obesity. We used 1H-NMR spectroscopy to study five glycoprotein variables, namely GlycA, GlycB, and GlycF and the height-to-width (H/W) ratio of GlycA and GlycB, in 17 women with PCOS (9 non-obese and 8 obese), 17 control women (9 non-obese and 8 obese), and 19 healthy men (10 non-obese and 9 obese). H/W ratios of GlycA and GlycB, but not glycoprotein areas, were specifically associated with PCOS independently of obesity. When considered as a whole, obese subjects presented higher GlycA, GlycB, and GlycF areas and higher H/W GlycA and GlycB ratios than their non-obese counterparts. All glycoprotein variables were associated with hsCRP, IL-6, and TNF-α, showing different correlations among PCOS, women, and men. Our present exploratory results suggest that 1H-NMR-derived glycoprotein profiles might serve as novel diagnostic markers of low-grade chronic inflammation in women with PCOS.

OBJECTIVE To investigate the metabolic and immunologic factors associated with the presence of central arterial stiffness as measured by the augmentation index (AIx). METHODS We conducted a cross-sectional study of 69 female patients with systemic lupus erythematosus (SLE) compared with a control group of 34 healthy women. The anthropometrical variables, the vascular studies, and the analytic data were obtained the same day. The AIx was assessed by peripheral arterial tonometry. The analysis of lipoprotein populations was performed using nuclear magnetic resonance (NMR) spectroscopy. RESULTS Arterial stiffness was increased in patients with SLE compared with control subjects (mean ± SD 20.30 ± 21.54% versus 10.84 ± 11.51%; P = 0.0021). Values for the AIx were correlated with the Framingham risk score (r = 0.481, P < 0.001), carotid intima-media thickness (r = 0.503, P < 0.001), systolic blood pressure (r = 0.270, P < 0.001), and age (r = 0.365, P < 0.001). Patients receiving antimalarial drugs had a lower AIx (mean ± SD 11.74 ± 11.28% versus 24.97 ± 20.63%; P = 0.024). The AIx was correlated with the atherogenic lipoproteins analyzed by NMR. The immunologic variables associated with the AIx were C4 (r = 0.259, P = 0.046) and IgM anti-β2 -glycoprotein I (IgM anti-β2 GPI) (r = 0.284, P = 0.284). In the multivariate analysis, age (β = 0.347, 95% confidence interval [95% CI] 0.020-0.669, P = 0.035), IgM β2 GPI (β = 0.321, 95% CI 0.024-0.618, P = 0.035) and small dense high-density lipoprotein (HDL) particles (β = 1.288, 95% CI 0.246-2.329, P = 0.017) predicted the AIx. CONCLUSION SLE patients had increased arterial stiffness compared with healthy control subjects. Arterial stiffness was decreased in patients treated with antimalarial drugs. Age, IgM β2 GPI, and the number of small dense HDL particles predicted the AIx.

This study evaluated the preclinical effect of obesity on the ventricular remodeling in adolescents with morbid obesity, and determined if subjects labelled as metabolically healthy obesity (MHO) presented better heart index than those with metabolically unhealthy obesity (MUO). Prospective case-control research of 45 adolescents (14-year-old) with morbid obesity and 25 normal weight adolescents' gender- and age-matched with Tanner stage 4-5. Left ventricle (LV) was evaluated by conventional Doppler echocardiography, tissue Doppler imaging and two-dimensional speckle tracking echocardiography. Compared to normal-weight subjects, adolescents with morbid obesity presented a high percentage of pathological LV geometry (87%; p0.01), and systolic and diastolic dysfunctions only detected by E/A ratio (2.0 vs 1.7, p0.01), global longitudinal strain (-21.0% vs -16.5%, p0.01), and early diastolic strain rate (3.2 vs 2.2, p0.01). A correlation was found between impaired cardiac index and body mass index (BMI), high blood pressure, hyperglycemia, low HDL-cholesterol and hypertriglyceridemia. BMI and HDL-cholesterol were the most significant independent variables. No significant differences were found in structural and functional cardiac index when MHO and MUO subjects were compared (global longitudinal strain: -17.0% vs -16.4%, p0.79). Morbidly obese adolescents have an abnormal LV geometry, closely related to BMI, and systolic and diastolic LV dysfunctions. Adolescents labelled as MHO, despite exhibiting better BMI and insulin-resistance values, present the same pathological heart changes as MUO.

Muscle is an essential organ for glucose metabolism and can be influenced by metabolic disorders and physical activity. Elevated muscle carnosine levels have been associated with insulin resistance and cardiometabolic risk factors. Little is known about muscle carnosine in type 1 diabetes (T1D) and how it is influenced by physical activity. The aim of this study was to characterize muscle carnosine in vivo by proton magnetic resonance spectroscopy (16 men with T1D (10 athletes/6 sedentary) and 14 controls without diabetes (9/5) were included. Body composition by DXA, cardiorespiratory capacity (VOSubjects with T1D presented higher carnosine CR levels compared to controls. T1D patients with a lower VOElevated muscle carnosine levels in persons with T1D and their effect on atherogenic lipoproteins can be modulated by physical activity.

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER). Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event (n = 125) and a group of control subjects (n = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipopro-teins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL parti-cles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.

Inflammation is a pathophysiological mechanism of atherosclerosis, and several mediators have been proposed as biomarkers. Acute-phase serum glycoproteins are upregulated in the liver during systemic inflammation. Because of their unique biochemical characteristics, they can be measured byWe recruited 295 FH patients (75.6% with FH-associated genetic variants). At baseline, a full glycoprotein profile, glycoprotein A and B (GlycA and B) concentrations and their height and width ratios (H/W) were analysed byAt baseline, the GlycA and GlycB concentrations and their H/W ratios were correlated with lipid profile and adiposity parameters, with the correlation between the GlycA and triglyceride concentrations (r = 0.780; p 0001) being the strongest. Glycoprotein concentrations were also correlated with inflammation markers, mainly hsCRP. Higher glycoprotein concentrations were observed in patients with higher intima media thickness, arterial rigidity and presence of arteriosclerotic plaques. In the multivariate and random forest analyses, the baseline GlycB concentration showed a significant contribution to the detection of FH individuals prone to develop carotid plaques.The concentrations of serum glycoproteins as assessed by

Patients with morbid obesity frequently present non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) associated with pro-atherogenic alterations. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for weight reduction, and for the remission of hepatic alterations. Using 1H-nuclear magnetic resonance (1H-NMR), we investigated the effects of LSG on lipoprotein and glycoprotein profile in patients with morbid obesity and liver disease. We included 154 patients with morbid obesity (49 non-NASH, 54 uncertain NASH, 51 definite NASH). A blood sample was obtained before surgery and, in patients with definite NASH, one year after surgery. Patients with NASH had increased concentrations of medium and small VLDL particles, VLDL and IDL cholesterol concentrations, IDL, LDL, and HDL triglyceride concentrations, and elevated glycoprotein levels. These changes were more marked in patients with type 2 diabetes mellitus. LSG produced significant decreases in the concentration of VLDL particles, VLDL cholesterol and triglycerides, an increase in the concentration LDL particles and LDL cholesterol concentrations, and a decrease in protein glycation. We conclude that patients with obesity and NASH had significant alterations in circulating levels of lipoproteins and glycoproteins that were associated with the severity of the disease. Most of these changes were reversed post-LSG.

Background Chronic kidney disease (CKD) patients have a high burden of atheromatous cardiovascular disease (ASCVD) not fully explained by traditional lipid parameters. Lipoprotein composition and subclass particle number information could improve ASCVD risk assessment. The objective of this study is to investigate the association of advanced lipoprotein parameters with the risk of atheromatosis in a subpopulation of the NEFRONA study. Methods This was a cross-sectional study in 395 non-diabetic individuals (209 CKD and 186 non-diabetic and non-CKD) without statin therapy. Vascular ultrasound examination assessing 10 territories was combined with advanced lipoprotein testing performed by nuclear magnetic resonance spectroscopy. Logistic regression was used to estimate adjusted odds ratios (ORs) per 1 standard deviation increment. Results Atheromatosis was more prevalent in CKD patients (33.9% versus 64.6%). After adjusting for age, gender, smoking habit and CKD stage, the amount of triglycerides (TGs) within low-density lipoprotein (LDL) lipoproteins was independently and positively associated with atheromatosis [OR 1.33; 95% confidence interval (CI) 1.03–1.74; P = 0.03]. Similarly, total and medium LDL particles (LDL-Ps) showed a positive association (OR 1.29; 95% CI 1.00–1.68; P = 0.05 and OR 1.34; 95% CI 1.04–1.75; P = 0.03, respectively). TG-loaded medium LDL-Ps were higher in CKD patients compared with controls and showed an adjusted OR of 1.40 (95% CI 1.09–1.82; P = 0.01) in non-diabetic patients (CKD and non-CKD individuals). In contrast, non-diabetic CKD patients showed a similar coefficient but the significance was lost (OR 1.2; 95% CI 0.8–1.7; P = 0.359). Conclusions Non-diabetic CKD patients showed a higher amount of TG-loaded medium LDL-Ps compared with controls. These particles were independently associated with atheromatosis in non-diabetic patients.

Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol content with cardiovascular (CV) death in chronic heart failure (HF) is lacking. To investigate the prognostic value of HDL-P size (HDL-Sz) and the number of cholesterol molecules per HDL-P for CV death in HF patients. Outpatient chronic HF patients were enrolled. Baseline HDL-P number, subfractions and HDL-Sz were measured using 1H-NMR spectroscopy. The HDL-C/P ratio was calculated as HDL-cholesterol over HDL-P. Endpoint was CV death, with non-CV death as the competing event. 422 patients were included and followed-up during a median of 4.1 (0–8) years. CV death occurred in 120 (30.5%) patients. Mean HDL-Sz was higher in CV dead as compared with survivors (8.39 nm vs. 8.31 nm, p

Background Abnormal lipid metabolism is observed in gestational diabetes mellitus (GDM) and in neonates with abnormal fetal growth, however, how these alterations specifically affect the umbilical cord blood lipoprotein profile is not well understood. Objective To assess the impact of GDM on the cord blood lipoprotein profile across birth-weight categories by using Advanced Lipoprotein Testing. Methods observational study involving 74 control and 62 GDM pregnant women and their offspring. Newborns were classified according to birth-weight as small (n = 39), adequate (n = 50) or large (n = 49) for gestational age (SGA, AGA and LGA, respectively). Two-dimensional diffusion-ordered 1H-NMR spectroscopy was used to profile umbilical cord serum lipoproteins. One hundred and three children were available in a two years follow-up study to evaluate associations between cord blood lipid profile and obesity. Results Baseline characteristics of the two groups were similar except for gestational weight gain. The size, lipid content, number and concentration of particles within their subclasses were similar between offspring born to GDM and control mothers. Using two-way analysis of variance, we observed an interaction between GDM and birth-weight categories for IDL-cholesterol content and IDL- and LDL-triglyceride content, and the number of medium VLDL and LDL particles, specifically in AGA neonates. Small LDL particles were independently associated with offspring obesity at two years. Conclusions In this selected cohort, GDM disturbs triglyceride and cholesterol lipoprotein content across birth-weight categories, and AGA neonates born to GDM mothers display a profile more similar to adults with dyslipidemia and atherosclerosis than to those born to mothers with normal glucose tolerance.

Introduction and objectives: Several types of lipoproteins beyond low-density lipoproteins (LDL) are causally related to cardiovascular disease. We aimed to analyze an advanced lipoprotein profile in individuals with normal and impaired glucose metabolism from different cohorts of a Mediterranean region. Methods: Cross-sectional study in 929 participants (463 normoglycemia, 250 prediabetes, and 216 type 2 diabetes mellitus) with normal renal function, free from cardiovascular disease, and without lipid-lowering treatment. Conventional and advanced (nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analyzed. Results: Compared with men, normoglycemic women showed lower serum triglyceride and LDL cholesterol concentrations, lower total LDL particles (P) as well as their subclasses and their cholesterol and triglyceride content, higher high-density lipoproteins (HDL)-P and all HDL-related variables (P < .05 for all comparisons). Compared with normoglycemic participants, diabetic participants showed higher large and small very LDL-P concentrations (P < .05) and lower total HDL-P and medium HDL-P concentrations (P < .05). Waist circumference and Fatty Liver Index were positively associated with a proatherogenic profile. Conclusions: Women had a better advanced lipoprotein profile than did men. Adiposity indexes related to insulin-resistance were positively associated with a proatherogenic lipid profile. NMR revealed altered lipoprotein particles other than LDL in participants with diabetes, frequently associated with an increased cardiovascular risk. Our findings support the usefulness of extended lipoprotein analysis by NMR spectroscopy to uncover new therapeutic targets to prevent cardiovascular events in at-risk participants. (C) 2021 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

This study aimed at evaluating the clinical relevance of glycoprotein profiles during the earliest phases of rheumatoid arthritis (RA) as biomarkers of cardiovascular (CV) risk and treatment response. Then, GlycA and GlycB serum levels were measured using 1H-nuclear magnetic resonance in 82 early RA patients, 14 clinically-suspect arthralgia (CSA), and 28 controls. Serum glycosyltransferase activity was assessed by a colorimetric assay. Subclinical CV disease was assessed by Doppler-ultrasound. We found that GlycA and GlycB serum levels were increased in RA (both p &lt, 0.001), but not in CSA, independently of cardiometabolic risk factors. Increased serum glycosyltransferase activity paralleled GlycA (r = 0.405, p &lt, 0.001) and GlycB levels (r = 0.327, p = 0.005) in RA. GlycA, but not GlycB, was associated with atherosclerosis occurrence (p = 0.012) and severity (p = 0.001). Adding GlycA to the mSCORE improved the identification of patients with atherosclerosis over mSCORE alone, increasing sensitivity (29.7 vs. 68.0%) and accuracy (55.8 vs. 76.6%) and allowing reclassification into more appropriate risk categories. GlycA-reclassification identified patients with impaired lipoprotein metabolism. Finally, baseline GlycA levels predicted poor clinical response upon anti-rheumatic treatment at 6 and 12 months in univariate and multivariate analysis. In sum, increased GlycA levels during the earliest stage of RA can be considered a powerful biomarker for CV risk stratification and treatment response.

Plasma glycoproteins are a composite biomarker of inflammation and can be detected by 1H-NMR. The aim of this study was to prospectively appraise the clinical value of plasma glycoproteins assessed by 1H-NMR in people living with HIV (PLWH). A total of 221 patients with HIV infection were recruited and studied at baseline and at 48 and 144 weeks. Patients were distributed into two groups according to baseline CD4+ T-cell number below or above 200 cells/&micro, L. Patients with fewer than 200 cells/&micro, L were distributed into the responders and nonresponders according to antiretroviral therapy (ART) response at 144 weeks. Glycoprotein concentrations were determined by 1H-NMR arising from the protein bond N-acetylglucosamine and N-acetylgalactosamine signals (GlycA), and N-acetylneuraminic acid signal (GlycB) associated with the sugar&ndash, protein bond concentration and aggregation state (shapes (height/width)). Basal glycoprotein concentrations were higher in patients with &lt, 200 CD4+ T-cell/&mu, L (Glyc A: 1040(917.9&ndash, 1199.1) vs. 950.4(845.5&ndash, 1050.9), p &lt, 0.001, and Glyc B: 521(440.3&ndash, 610.3) vs. 468.6(417.9&ndash, 507.0) &mu, mol/L, p &lt, 0.001) being reduced by ART. The height/width (H/W) ratio was the parameter showing a better association with this clinical status. Baseline glycoproteins predict the condition of responder/nonresponder. In this study, 1H-NMR glycoproteins provide novel insights to assess inflammation status and have prognostic value in PLWH.

Acute-phase glycoprotein 1H-NMR spectroscopy profiles serve as surrogate markers of chronic inflammation in metabolic disorders such as obesity, diabetes and polycystic ovary syndrome (PCOS). The latter is associated with increased height-to-width (H/W) ratios of GlycA and GlycB after fasting, but not to glycoprotein areas, regardless of obesity. We studied the responses to separate glucose, lipid and protein oral challenges of five glycoprotein variables (GlycA, GlycB, and GlycF areas and the GlycA and GlycB H/W ratios) in 17 women with PCOS, 17 control women, and 19 healthy men. Glucose and protein ingestion resulted into decreases in all glycoprotein variables, whereas lipid ingestion increased GlycA, GlycF and induced minimal changes in GlycB and GlycB H/W. We found no effects of obesity or group of subjects on postprandial glycoprotein variables regardless of the macronutrient being ingested. However, a statistically significant interaction indicated that obesity blunted the decrease in some of these variables in control women and men, whereas obese women with PCOS showed larger changes when compared with their non-obese counterparts. In conclusion, acute-phase glycoprotein profiles indicate an anti-inflammatory response during postprandial phase that is less pronounced after lipid ingestion, and is counteracted by the chronic inflammatory background associated with obesity and PCOS.

Plasma glycoproteins are a composite biomarker of inflammation and can be detected by 1H-NMR. The aim of this study was to prospectively appraise the clinical value of plasma glycoproteins assessed by 1H-NMR in people living with HIV (PLWH). A total of 221 patients with HIV infection were recruited and studied at baseline and at 48 and 144 weeks. Patients were distributed into two groups according to baseline CD4+ T-cell number below or above 200 cells/µL. Patients with fewer than 200 cells/µL were distributed into the responders and nonresponders according to antiretroviral therapy (ART) response at 144 weeks. Glycoprotein concentrations were determined by 1H-NMR arising from the protein bond N-acetylglucosamine and N-acetylgalactosamine signals (GlycA); and N-acetylneuraminic acid signal (GlycB) associated with the sugar–protein bond concentration and aggregation state (shapes (height/width)). Basal glycoprotein concentrations were higher in patients with < 200 CD4+ T-cell/μL (Glyc A: 1040(917.9–1199.1) vs. 950.4(845.5–1050.9), p < 0.001, and Glyc B: 521(440.3–610.3) vs. 468.6(417.9–507.0) μ mol/L, p < 0.001) being reduced by ART. The height/width (H/W) ratio was the parameter showing a better association with this clinical status. Baseline glycoproteins predict the condition of responder/nonresponder. In this study, 1H-NMR glycoproteins provide novel insights to assess inflammation status and have prognostic value in PLWH.

BACKGROUND There is growing evidence that oxidative stress (OS) is a critical factor linking obesity with its associated comorbidities, such as cardiovascular diseases. AIM To evaluate the degree of OS in people with morbid obesity and its relationship with glycoproteins, determined using 1H-NMR spectroscopy, before and after bariatric surgery (BS). METHODS In this observational cohort study, plasma from 24 patients with BMI ≥ 40 kg/m2 (age: 21-65 years) was used to measure metabolites implicated in OS. We measured glycoprotein (GlycA, GlycB and GlycF) areas and shape factors (H/W = height/width). RESULTS One year after BS, oxidized low-density lipoprotein had decreased by 49% (P