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1.
Laparoscopic sleeve gastrectomy alters 1H-NMR-measured lipoprotein and glycoprotein profile in patients with severe obesity and nonalcoholic fatty liver disease.
Cabré, N, Gil, M, Amigó, N, Luciano-Mateo, F, Baiges-Gaya, G, Fernández-Arroyo, S, Rodríguez-Tomàs, E, Hernández-Aguilera, A, Castañé, H, París, M, et al
Scientific reports. 2021;(1):1343
Abstract
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.
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2.
Nuclear Magnetic Resonance Derived Biomarkers for Evaluating Cardiometabolic Risk in Youth and Young Adults Across the Spectrum of Glucose Tolerance.
Chung, ST, Matta, ST, Meyers, AG, Cravalho, CK, Villalobos-Perez, A, Dawson, JM, Sharma, VR, Sampson, ML, Otvos, JD, Magge, SN
Frontiers in endocrinology. 2021;:665292
Abstract
UNLABELLED Youth with obesity have an increased risk for cardiometabolic disease, but identifying those at highest risk remains a challenge. Four biomarkers that might serve this purpose are "by products" of clinical NMR LipoProfile® lipid testing: LPIR (Lipoprotein Insulin Resistance Index), GlycA (inflammation marker), BCAA (total branched-chain amino acids), and glycine. All are strongly related to insulin resistance and type 2 diabetes (T2DM) in adults (glycine inversely) and are independent of biological and methodological variations in insulin assays. However, their clinical utility in youth is unclear. We compared fasting levels of these biomarkers in 186 youth (42 lean normal glucose tolerant (NGT), 88 obese NGT, 23 with prediabetes (PreDM), and 33 with T2DM. All four biomarkers were associated with obesity and glycemia in youth. LPIR and GlycA were highest in youth with PreDM and T2DM, whereas glycine was lowest in youth with T2DM. While all four were correlated with HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), LPIR had the strongest correlation (LPIR: r = 0.6; GlycA: r = 0.4, glycine: r = -0.4, BCAA r = 0.2, all P < 0.01). All four markers correlated with HbA1c (LPIR, GlycA, BCAA r ≥ 0.3 and glycine: r = -0.3, all P < 0.001). In multi-variable regression models, LPIR, GlycA, and glycine were independently associated with HOMA-IR (Adjusted R2 = 0.473, P < 0.001) and LPIR, glycine, and BCAA were independently associated with HbA1c (Adjusted R2 = 0.33, P < 0.001). An LPIR index of >44 was associated with elevated blood pressure, BMI, and dyslipidemia. Plasma NMR-derived markers were related to adverse markers of cardiometabolic risk in youth. LPIR, either alone or in combination with GlycA, should be explored as a non-insulin dependent predictive tool for development of insulin resistance and diabetes in youth. CLINICAL TRIAL REGISTRATION Clinicaltrials.gov, identifier NCT:02960659.
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3.
Effects of Walnut Consumption for 2 Years on Lipoprotein Subclasses Among Healthy Elders: Findings From the WAHA Randomized Controlled Trial.
Rajaram, S, Cofán, M, Sala-Vila, A, Haddad, E, Serra-Mir, M, Bitok, E, Roth, I, Freitas-Simoes, TM, Kaur, A, Valls-Pedret, C, et al
Circulation. 2021;(13):1083-1085
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4.
Main differences between two highly effective lipid-lowering therapies in subclasses of lipoproteins in patients with acute myocardial infarction.
Pinto, LCS, Mello, APQ, Izar, MCO, Damasceno, NRT, Neto, AMF, França, CN, Caixeta, A, Bianco, HT, Póvoa, RMS, Moreira, FT, et al
Lipids in health and disease. 2021;(1):124
Abstract
BACKGROUND Large observational studies have shown that small, dense LDL subfractions are related to atherosclerotic cardiovascular disease. This study assessed the effects of two highly effective lipid-lowering therapies in the atherogenic subclasses of lipoproteins in subjects with ST-segment elevation myocardial infarction (STEMI). METHODS Patients of both sexes admitted with their first myocardial infarction and submitted to pharmacoinvasive strategy (N = 101) were included and randomized using a central computerized system to receive a daily dose of simvastatin 40 mg plus ezetimibe 10 mg or rosuvastatin 20 mg for 30 days. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) subfractions were analysed by polyacrylamide gel electrophoresis (Lipoprint System) on the first (D1) and 30th days (D30) of lipid-lowering therapy. Changes in LDL and IDL subfractions between D1 and D30 were compared between the lipid-lowering therapies (Mann-Whitney U test). RESULTS The classic lipid profile was similar in both therapy arms at D1 and D30. At D30, the achievement of lipid goals was comparable between lipid-lowering therapies. Cholesterol content in atherogenic subclasses of LDL (p = 0.043) and IDL (p = 0.047) decreased more efficiently with simvastatin plus ezetimibe than with rosuvastatin. CONCLUSIONS Lipid-lowering therapy with simvastatin plus ezetimibe was associated with a better pattern of lipoprotein subfractions than rosuvastatin monotherapy. This finding was noted despite similar effects in the classic lipid profile and may contribute to residual cardiovascular risk. TRIAL REGISTRATION ClinicalTrials.gov , NCT02428374, registered on 28/09/2014.
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5.
Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies.
Daviglus, ML, Ferdinand, KC, López, JAG, Wu, Y, Monsalvo, ML, Rodriguez, CJ
Journal of the American Heart Association. 2021;(1):e016839
Abstract
Background Prevalence of cardiovascular disease risk factors and rates of atherosclerotic cardiovascular disease outcomes vary across racial/ethnic groups. This analysis examined the effects of evolocumab on LDL-C (low-density lipoprotein cholesterol) levels and LDL-C goals achievement by race/ethnicity. Methods and Results Data from 15 phase 2 and 3 studies of treatment with evolocumab versus placebo or ezetimibe were pooled (n=7669). Results were analyzed by participant clinical characteristics and by self-identified race/ethnicity. Key outcomes included percent change from baseline in LDL-C, achievement of LDL-C <70 mg/dL, and LDL-C reduction of ≥50% at 12 weeks and at 1 to 5 years. Across 12-week studies, mean percent change in LDL-C from baseline in evolocumab-treated participants was -52% to -59% for White and -46% to -67% for non-White participants, across clinical characteristics groups. LDL-C <70 mg/dL was achieved in 43% to 84% and 62% to 94% and LDL-C reduction of ≥50% in 63% to 78% and 58% to 86%, respectively. In 1- to 5-year studies, mean percent change in LDL-C was -46% to -52% for White and -49% to -55% for non-White participants. LDL-C <70 mg/dL was achieved in 53% to 84% and 66% to 77%, and LDL-C reduction of ≥50% in 53% to 67% and 58% to 68%, respectively. The treatment effect on mean percent change in LDL-C differed only in participants with type 2 diabetes mellitus, with a larger reduction in Asian participants. The qualitative interaction P values were nonsignificant, indicating consistent directionality of effect. Conclusions Similar reduction in LDL-C levels with evolocumab was observed across racial/ethnic groups in 12-week and 1- to 5-year studies. Among those with diabetes mellitus, Asian participants had greater LDL-C reduction.
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6.
New Therapies for Lowering Triglyceride-Rich Lipoproteins: JACC Focus Seminar 3/4.
Rosenson, RS, Shaik, A, Song, W
Journal of the American College of Cardiology. 2021;(18):1817-1830
Abstract
Emerging evidence suggests that elevated concentrations of triglyceride-rich lipoprotein remnants (TRLs) derived from hepatic and intestinal sources contribute to the risk of atherosclerotic cardiovascular events. Natural selection studies support a causal role for elevated concentrations of remnant cholesterol and the pathways contributing to perturbations in metabolic pathways regulating TRLs with an increased risk of atherosclerotic cardiovascular disease events. New therapies targeting select catalytic pathways in TRL metabolism reduce atherosclerosis in experimental models, and concentrations of TRLs in patients with a vast range of triglyceride levels. Clinical trials with inhibitors of angiopoietin-like 3 protein and apolipoprotein C-III will be required to provide further guidance on the potential contribution of these emerging therapies in the paradigm of cardiovascular risk management in patients with elevated remnant cholesterol.
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7.
The surface lipoproteins of gram-negative bacteria: Protectors and foragers in harsh environments.
Cole, GB, Bateman, TJ, Moraes, TF
The Journal of biological chemistry. 2021;:100147
Abstract
Gram-negative pathogens are enveloped by an outer membrane that serves as a double-edged sword: On the one hand, it provides a layer of protection for the bacterium from environmental insults, including other bacteria and the host immune system. On the other hand, it restricts movement of vital nutrients into the cell and provides a plethora of antigens that can be detected by host immune systems. One strategy used to overcome these limitations is the decoration of the outer surface of gram-negative bacteria with proteins tethered to the outer membrane through a lipid anchor. These surface lipoproteins (SLPs) fulfill critical roles in immune evasion and nutrient acquisition, but as more bacterial genomes are sequenced, we are beginning to discover their prevalence and their different roles and mechanisms and importantly how we can exploit them as antimicrobial targets. This review will focus on representative SLPs that gram-negative bacteria use to overcome host innate immunity, specifically the areas of nutritional immunity and complement system evasion. We elaborate on the structures of some notable SLPs required for binding target molecules in hosts and how this information can be used alongside bioinformatics to understand mechanisms of binding and in the discovery of new SLPs. This information provides a foundation for the development of therapeutics and the design of vaccine antigens.
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8.
Persistence of Lipoproteins and Cholesterol Alterations after Sepsis: Implication for Atherosclerosis Progression.
Laudanski, K
International journal of molecular sciences. 2021;(19)
Abstract
(1) Background: Sepsis is one of the most common critical care illnesses with increasing survivorship. The quality of life in sepsis survivors is adversely affected by several co-morbidities, including increased incidence of dementia, stroke, cardiac disease and at least temporary deterioration in cognitive dysfunction. One of the potential explanations for their progression is the persistence of lipid profile abnormalities induced during acute sepsis into recovery, resulting in acceleration of atherosclerosis. (2) Methods: This is a targeted review of the abnormalities in the long-term lipid profile abnormalities after sepsis; (3) Results: There is a well-established body of evidence demonstrating acute alteration in lipid profile (HDL-c ↓↓, LDL-C -c ↓↓). In contrast, a limited number of studies demonstrated depression of HDL-c levels with a concomitant increase in LDL-C -c in the wake of sepsis. VLDL-C -c and Lp(a) remained unaltered in few studies as well. Apolipoprotein A1 was altered in survivors suggesting abnormalities in lipoprotein metabolism concomitant to overall lipoprotein abnormalities. However, most of the studies were limited to a four-month follow-up and patient groups were relatively small. Only one study looked at the atherosclerosis progression in sepsis survivors using clinical correlates, demonstrating an acceleration of plaque formation in the aorta, and a large metanalysis suggested an increase in the risk of stroke or acute coronary event between 3% to 9% in sepsis survivors. (4) Conclusions: The limited evidence suggests an emergence and persistence of the proatherogenic lipid profile in sepsis survivors that potentially contributes, along with other factors, to the clinical sequel of atherosclerosis.
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9.
Evaluation of atherogenic lipoprotein-cholesterol to HDL cholesterol ratio as a prognostic test for ST-segment elevation myocardial infarction.
Li, JY, Xu, WJ, Zhou, Z, Zhang, RL, Sun, T, Xu, H, Wu, J
International journal of medical sciences. 2021;(13):2897-2904
Abstract
Background: The detectable component of triglyceride-rich lipoproteins (TGRLs), remnant lipoprotein cholesterol (RLP-c), has been proven being correlated with the progression of atherosclerosis and myocardial infarction. However, when taken as a risk predictor, the prognostic and diagnostic potential of RLP-c remains controversial in studies. In this study, we evaluated the hypothesis that atherogenic lipoprotein-cholesterol (AL-c), representing the sum of RLP-c and the sd-LDL-c, to the HDL-c ratio, could represent a better predictive indicator than RLP-c alone in ST-segment elevation myocardial infarction (STEMI). Methods: The 316 consecutive patients suffering from persistent chest discomfort admitted to the Shanghai General Hospital between January 2018 and June 2018 were enrolled. 149 STEMI patients (62% men, mean age 69.6 ± 13.3 years) were included as the study cohort. The AL-c/HDL-c ratio was calculated on admission in a cohort of electrocardiogram-confirmed STEMI patients and compared to other lipid profiles as a predictive indicator. Results: The AL-c/HDL-c ratio was significantly increased in STEMI patients compared with apparently healthy adults (0.93; IQR [0.71-1.18] vs 0.70; IQR [0.45-1.04]; p < 0.001). Gender dependency existed, and the male and female patients had median AL-c/HDL-c ratios of 1.01 and 0.79, respectively (p < 0.001). Compared to RLP-c, the AL-c/HDL-c ratio had a better prognostic value to predict STEMI risk in both sexes (AUC of 0.672 with a sensitivity of 0.794 in males and 0.613 with a sensitivity of 0.684 in females). Conclusions: The AL-c/HDL-c ratio could represent a convenient and sensitive biomarker for screening and predicting STEMI risk.
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10.
Changes in serum lipid levels during pregnancy in women with gestational diabetes. A narrative review.
Cibickova, L, Schovanek, J, Karasek, D
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2021;(1):8-12
Abstract
We review current knowledge on lipid metabolism changes during pregnancy with special focus on changes in gestational diabetes. In physiological pregnancy, total plasma cholesterol, triglyceride and HDL-cholesterol level rises, the atherogenic index (LDL-cholesterol / HDL-cholesterol remains unchanged. Compared with healthy women, women with GDM show more pronounced signs of mixed dyslipidaemia - increased levels of triglyceride, changes in cholesterol and lipoprotein concentrations with a shift towards greater small dense LDL subtractions, which is typical for insulin resistance states. Dyslipidaemia, particularly hypertriglyceridemia, is thought to be one of the key drivers of foetal macrosomia and that is why measurements of plasma lipids may be valuable in detecting the metabolic abnormality in GDM and in predicting foetal outcome. Dyslipidaemia in GDM is seen as proatherogenic and potentially harmful for the baby and therefore it should be monitored more carefully.